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  • Acanthamoeba castellanii phosphate transporter (AcPHS) is important to maintain inorganic phosphate influx and is related to trophozoite metabolic processes
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2020-01-21
    Luiz Fernando Carvalho-Kelly, Clara Ferreira Pralon, Nathalia Rocco-Machado, Michelle Tanny Nascimento, Ayra Diandra Carvalho-de-Araújo, José Roberto Meyer-Fernandes

    Abstract Acanthamoeba castellanii is a free-living amoeba and the etiological agent of granulomatous amoebic encephalitis and amoebic keratitis. A. castellanii can be present as trophozoites or cysts. The trophozoite is the vegetative form of the cell and has great infective capacity compared to the cysts, which are the dormant form that protect the cell from environmental changes. Phosphate transporters are a group of proteins that are able to internalize inorganic phosphate from the extracellular to intracellular medium. Plasma membrane phosphate transporters are responsible for maintaining phosphate homeostasis, and in some organisms, regulating cellular growth. The aim of this work was to biochemically characterize the plasma membrane phosphate transporter in A. castellanii and its role in cellular growth and metabolism. To measure inorganic phosphate (Pi) uptake, trophozoites were grown in liquid PYG medium at 28 °C for 2 days. The phosphate uptake was measured by the rapid filtration of intact cells incubated with 0.5 μCi of 32Pi for 1 h. The Pi transport was linear as a function of time and exhibited Michaelis-Menten kinetics with a Km = 88.78 ± 6.86 μM Pi and Vmax = 547.5 ± 16.9 Pi × h−1 × 10−6 cells. A. castellanii presented linear phosphate uptake up to 1 h with a cell density ranging from 1 × 105 to 2 × 106 amoeba × ml−1. The Pi uptake was higher in the acidic pH range than in the alkaline range. The oxygen consumption of living trophozoites increased according to Pi addition to the extracellular medium. When the cells were treated with FCCP, no effect from Pi on the oxygen flow was observed. The addition of increasing Pi concentrations not only increased oxygen consumption but also increased the intracellular ATP pool. These phenomena were abolished when the cells were treated with FCCP or exposed to hypoxia. Together, these results reinforce the hypothesis that Pi is a key nutrient for Acanthamoeba castellanii metabolism.

    更新日期:2020-01-22
  • Artesunate targets oral tongue squamous cell carcinoma via mitochondrial dysfunction-dependent oxidative damage and Akt/AMPK/mTOR inhibition
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2020-01-21
    Qingfeng Xiao, Lei Yang, Hao Hu, Yue Ke

    Abstract Although mitochondrial metabolism has recently gained attention as a promising therapeutic strategy in cancer, little is known on the impact of mitochondrial respiration inhibition on oral tongue squamous cell carcinoma (OTSCC). Using in vitro and in vivo OTSCC models, our work demonstrates that inducing mitochondrial dysfunction by anti-malarial drug artesunate is effective in targeting OTSCC stem-cell like and bulk cells. Artesunate inhibits anchorage-independent colony formation, proliferation and survival in all tested OTSCC cell lines although with varying efficacy. Artesunate displays preferential anti-OTSCC activity by sparing normal cells. Mechanism analysis indicates that artesunate inhibits mitochondrial respiration via suppressing mitochondrial complex I and II but not IV or V, resulting in oxidative stress and damage. Interestingly, OTSCC cells that are more sensitive to artesunate have higher level of basal mitochondrial respiration and reversed respiratory capacity compared to those with less sensitivity to artesunate, suggesting the varying dependence on mitochondrial respiration among OTSCC cell lines. In addition, artesunate induces oxidative stress and damage in cells with low sensitivity to a less extent than in those with high sensitivity. We confirm that mitochondrial respiration inhibition is required for the action of artesunate in OTSCC. Mitochondrial dysfunction by artesunate further activates AMPK and suppresses Akt/mTOR. Importantly, the in vitro observations are reproducible in vivo OTSCC xenograft mouse model. Our findings provide pre-clinical evidence on the efficacy of artesunate and emphasize the therapeutic value of targeting mitochondrial respiration in OTSCC.

    更新日期:2020-01-22
  • Effect of methyl jasmonate and 3-bromopyruvate combination therapy on mice bearing the 4 T1 breast cancer cell line
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2020-01-20
    Somayeh Yousefi, Parisa Darvishi, Zeynab Yousefi, Ali Akbar Pourfathollah

    Abstract Cancer cells apply the Warburg pathway to meet their increased metabolic demands caused by their rapid growth and proliferation and also creates an acidic environment to promote cancer cell invasion. 3-bromopyruvate (3-BrP) as an anti-cancer agent disrupts glycolytic pathway. Moreover, one of the mechanism of actions of Methyl Jasmonate (MJ) is interference in glycolysis. Hence, the aim of this study was to evaluate MJ and 3-BrP interaction. MTT assay was used to determine IC50 and synergistic concentrations. Combination index was applied to evaluate the drug- drug interaction. Human tumor xenograft breast cancer mice was used to evaluate drug efficacy in vivo. Tumor size was considered as a drug efficacy criterion. In addition to drug efficacy, probable side effects of these drugs including hepatotoxicity, renal failure, immunotoxicity, and losing weight were evaluated. Serum alanine aminotransferase and aspartate aminotransferase for hepatotoxicity, serum urea and creatinine level for the possibility of renal failure and changes in body weight were measured to evaluate drug toxicity. IL10 and TGFβ secretion in supernatant of isolated splenocytes from treated mice were assessed to check immunotoxicity. 3-BrP synergistically augmented the efficacy of MJ in the specific concentrations. This polytherapy was more effective than monotherapy of 3-BrP, MJ, and also surprisingly cyclophosphamide as a routine treatment for breast cancer in the tumor bearing mice. These results have been shown by decrease in tumor volume and increase of tumor growth inhibition percentage. This combination therapy didn’t have any noticeable side effects on kidney, liver, and immune system and body weight.

    更新日期:2020-01-21
  • Kinetics simulation of transmembrane transport of ions and molecules through a semipermeable membrane
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2020-01-13
    S. O. Karakhim, P. F. Zhuk, S. O. Kosterin

    Abstract We have developed a model to study the kinetics of the redistribution of ions and molecules through a semipermeable membrane in complex mixtures of substances penetrating and nonpenetrating through a membrane. It takes into account the degree of dissociation of these substances, their initial concentrations in solutions separated by a membrane, and volumes of these solutions. The model is based on the assumption that only uncharged particles (molecules or ion pairs) diffuse through a membrane (and not ions as in the Donnan model). The developed model makes it possible to calculate the temporal dependencies of concentrations for all processing ions and molecules at system transition from the initial state to equilibrium. Under equilibrium conditions, the ratio of ion concentrations in solutions separated by a membrane obeys the Donnan distribution. The Donnan effect is the result of three factors: equality of equilibrium concentrations of penetrating molecules on each side of a membrane, dissociation of molecules into ions, and Le Chatelier’s principle. It is shown that the Donnan distribution (irregularity of ion distribution) and accordingly absolute value of the Donnan membrane potential increases if: (i) the nonpenetrating salt concentration (in one of the solutions) and its dissociation constant increases, (ii) the total penetrating salt concentration and its dissociation constant decreases, and (iii) the volumes ratio increases (between solutions with and without a nonpenetrating substance). It is shown also that only a slight difference between the degrees of dissociation of two substances can be used for their membrane separation.

    更新日期:2020-01-14
  • The lncRNA FAL1 protects against hypoxia-reoxygenation- induced brain endothelial damages through regulating PAK1
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2020-01-11
    Mingqing Gao, Jieting Fu, Yanqiang Wang

    Dysregulation of cerebral microvascular endothelial cells plays an important role in the pathogenesis of stroke. However, the underlying mechanisms still need to be elucidated. In the current study, we found that the long non-coding RNA (lncRNA) FAL1 was significantly reduced in response to oxygen-glucose deprivation and reoxygenation (OGD/R) stimulation in human primary brain microvascular endothelial cells (HBMVECs). Interestingly, overexpression of FAL1 ameliorated OGD/R-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and increasing the level of reduced glutathione (GSH). Also, overexpression of FAL1 suppressed OGD/R-induced secretions of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and high mobility group box-1 (HMGB-1). We then found that OGD/R-induced reduction of cell viability and release of lactate dehydrogenase (LDH) were prevented by overexpression of FAL1. Additionally, exposure to OGD/R significantly reduced the phosphorylated levels of PAK1 and AKT as well as the total level of proliferating cell nuclear antigen (PCNA), which was restored by overexpression of FAL1. Importantly, overexpression of FAL1 restored OGD/R-induced reduction in the expression of endothelial nitric oxide synthase (eNOS) and the subsequent release of nitric oxide (NO). Our results implicate that FAL1 might be involved in the process of brain endothelial cell damage.

    更新日期:2020-01-13
  • Fatty acid synthesis by Chlamydomonas reinhardtii in phosphorus limitation
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2020-01-04
    Huda A Qari, Mohammad Oves

    Abstract The importance of crucial nutrient factors like Phosphate (P) and their limited availability leads to variable fluctuations in fatty acid and phospholipid synthesis in the green alga. These fatty acids and phospholipids are an imperative byproduct of alga which used in biofuel production. The production of phospholipids in alga might be naturally enhanced by the optimized supplied by specific essential nutrient like Phosphate. In this study, green alga Chlamydomonas reinhardtii was cultivated in phosphate stress condition to obtain maximum phospholipids. In the stress condition, the organism exhibited variable changes in chlorophyll, fatty acid, and phospholipid compositions. These parameters analyzed by biomass, X-ray, GC, and TLC. Remarkably, saturated fatty acids, monounsaturated, and di-unsaturated fatty acids amounts, increases, while polyunsaturated fatty acids to decrease markedly. The maximum fatty acid content observed at 0.4 mgl−1 P content in growing media. A broad peak area of 56% of hexadecanoic acid (C 16:0) and followed by 28.8% linolenic (C18:3) was observed in GC analysis. These results indicate the essential fatty acid accumulation maximized at particular phosphate concentration in growing media. This necessary and essential fatty acid production from green algae in a sustainable manner is an inexpensive and excellent way for commercialization and biofuel production.

    更新日期:2020-01-04
  • Radioprotective effect of diethylcarbamazine on radiation-induced acute lung injury and oxidative stress in mice
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-12-18
    Soghra Farzipour, Fereshteh Talebpour Amiri, Ehsan Mihandoust, Fatemeh Shaki, Zohreh Noaparast, Arash Ghasemi, Seyed Jalal Hosseinimehr

    The present study was designed to evaluate the radioprotective effect of diethylcarbamazine (DEC) against oxidative stress and acute lung injury induced by total body radiation (TBI) in mice. For study the optimum dose for radiation protection of DEC, mice were administrated with three dose of DEC (10, 50 and 100 mg/kg), once daily for eight consecutive days. Animals were exposed whole body to 5 Gy X-radiation on the 9 day. The radioprotective potential of DEC in lung tissues was assessed using oxidative stress examinations at 24 h after TBI and histopathological assay also was analyzed one week after TBI. Results from biochemical analyses demonstrated increased malonyldialdehyde (MDA), nitric oxide (NO) and protein carbonyl (PC) levels of lung tissues in only irradiated group. Histopathologic findings also showed an increase in the number of inflammatory cells and the acute lung injury in this group. DEC pretreatment significantly mitigated the oxidative stress biomarkers as well as histological damages in irradiated mice. The favorable radioprotective effect against lungs injury was observed at a dose of 10 mg/kg of DEC in mice as compared with two other doses (50 and 100 mg/kg). The data of this study showed that DEC at a dose of 10 mg/kg with having antioxidant and anti-inflammatory properties can be used as a therapeutic candidate for protecting the lung from radiation-induced damage.

    更新日期:2019-12-19
  • Energization by multiple substrates and calcium challenge reveal dysfunctions in brain mitochondria in a model related to acute psychosis
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-12-18
    Jamila Monteiro, Gabriela Assis-de-Lemos, Eduardo de-Souza-Ferreira, Adriana M. Marques, Gilda A. Neves, Mariana S. Silveira, Antonio Galina

    Schizophrenia etiology is unknown, nevertheless imbalances occurring in an acute psychotic episode are important to its development, such as alterations in cellular energetic state, REDOX homeostasis and intracellular Ca2+ management, all of which are controlled primarily by mitochondria. However, mitochondrial function was always evaluated singularly, in the presence of specific respiratory substrates, without considering the plurality of the electron transport system. In this study, mitochondrial function was analyzed under conditions of isolated or multiple respiratory substrates using brain mitochondria isolated from MK-801-exposed mice. Results showed a high H2O2 production in the presence of pyruvate/malate, with no change in oxygen consumption. In the condition of multiple substrates, however, this effect is lost. The analysis of Ca2+ retention capacity revealed a significant change in the uptake kinetics of this ion by mitochondria in MK-801-exposed animals. Futhermore, when mitochondria were exposed to calcium, a total loss of oxidative phosphorylation and an impressive increase in H2O2 production were observed in the condition of multiple substrates. There was no alteration in the activity of the antioxidant enzymes analyzed. The data demonstrate for the first time, in an animal model of psychosis, two important aspects (1) mitochondria may compensate deficiencies in a single mitochondrial complex when they oxidize several substrates simultaneously, (2) Ca2+ handling is compromised in MK-801-exposed mice, resulting in a loss of phosphorylative capacity and an increase in H2O2 production. These data favor the hypothesis that disruption of key physiological roles of mitochondria may be a trigger in acute psychosis and, consequently, schizophrenia.

    更新日期:2019-12-19
  • Farnesol contributes to intestinal epithelial barrier function by enhancing tight junctions via the JAK/STAT3 signaling pathway in differentiated Caco-2 cells
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-12-16
    Yangxin Fang, Chunrong Wu, Qiuyue Wang, Jianguo Tang

    Candida albicans causes mucosal diseases and secretes farnesol, a quorum-sensing molecule, which plays a vital role in suppressing the yeast-to-mycelia switch. Farnesol can also regulate immune cell function. However, how farnesol interacts with the intestinal epithelium remains unknown. Herein, we identified that farnesol promotes intestinal barrier function, by promoting transepithelial electrical resistance, reducing paracellular flux, inducing the Zonula Occludens-1 Protein (ZO-1) and occludin expression. Moreover, the JAK/STAT3 signaling pathway was activated after farnesol treatment, and inhibition of STAT3 phosphorylation by stattic remarkably suppressed the expression level of ZO-1. Additionally, chromatin immunoprecipitation assay (Chip) revealed that farnesol facilitated the transcriptional activation of STAT3 to significantly enhance the expression of ZO-1. Taken together, our findings demonstrated that farnesol facilitated intestinal epithelial barrier transcriptional regulation via activating JAK/STAT3 signaling. The involved molecules may be potentially targeted for treatment of Candida albicans invasion.

    更新日期:2019-12-17
  • Correction to: BIOMEMBRANES 2018
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-12-06
    E. Skorova, E. Petersen, E. Shabalina

    This research was supported by RSF grant (No. 18-15-00391).

    更新日期:2019-12-07
  • The lncRNA ROR/miR-124-3p/TRAF6 axis regulated the ischaemia reperfusion injury-induced inflammatory response in human cardiac myocytes
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-11-25
    Ying-Ping Liang, Qin Liu, Guo-Hai Xu, Jing Zhang, Yong Chen, Fu-Zhou Hua, Chang-Qing Deng, Yan-Hui Hu

    Myocardial ischaemia reperfusion injury (MIRI) is considered the primary cause of death in patients with cardiovascular diseases. Recently, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be involved in the pathogenesis of MIRI. However, whether lncRNA ROR and miR-124-3p play roles in MIRI and the underlying mechanism remain undetermined. HCMs were exposed to hypoxic conditions for 2 h followed by re-oxygenation (H/R) treatment. Expression of miR-124-3p and lncRNA ROR in HCMs was measured by qRT-PCR. TRAF6 expression was evaluated by qRT-PCR and western blotting. ELISA and qRT-PCR were conducted to assess the production of TNF-α, IL-6, and IL-1β. The interaction between miR-124-3p and TRAF6, as well as between miR-124-3p and lncRNA ROR, was verified by dual-luciferase reporter assay. Cell apoptosis was detected by flow cytometry analysis. Our data revealed that miR-124-3p was significantly downregulated, while TRAF6 and lncRNA ROR were upregulated in both MIRI rat model and H/R treated HCMs. Overexpression of miR-124-3p reversed the H/R-induced cell apoptosis and upregulation of TNF-α, IL-6, and IL-1β. Mechanistically, miR-124-3p bound and negatively regulated TRAF6 expression in HCMs. Moreover, TRAF6 overexpression significantly blocked the effects of miR-124-3p mimics on cell apoptosis and inflammatory response of HCMs, which involved the NF-κB pathway. Further analysis showed that lncRNA ROR sponged and negatively regulated miR-124-3p in HCMs. Overexpression of IL-1β was demonstrated to promote H/R induced cell apoptosis in HCMs. In addition, overexpression of ROR further enhanced the H/R-induced inflammation and cell apoptosis through its action on miR-124-3p. The lncRNA ROR/miR-124-3p/TRAF6 axis regulated the H/R-induced cell apoptosis and inflammatory response of HCMs.

    更新日期:2019-11-26
  • Effect of hydrogen-rich water on the Nrf2/ARE signaling pathway in rats with myocardial ischemia-reperfusion injury
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-11-25
    Liangtong Li, Tongtong Liu, Li Liu, Shaochun Li, Zhe Zhang, Ruisha Zhang, Yujuan Zhou, Fulin Liu

    The effects of hydrogen-rich water on oxidative stress via the Nrf2/ARE signaling pathway were studied in rats with myocardial ischemia-reperfusion injury (MIRI). Sixty rats were randomly divided into a hydrogen-rich water group and a control group, with 30 rats in each group. The two groups were randomly divided into three groups: pre-ischemic period, ischemic period and reperfusion period. After the heart was removed, it was fixed in a Langendorff device and perfused with an oxygen-balanced 37 °C perfusate. The control group was perfused with Kreb’s-Ringers (K-R) solution, and the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. The levels of mRNA and protein of Nrf2, NQO1, HO-1 and SOD-1 in cardiomyocytes were detected by RT-qPCR, immunohistochemistry (IHC) and Western blot analysis. SOD activity and MDA content were determined. Hydrogen-rich water increased the activation of the Nrf2/ARE signaling pathway, and the levels of mRNA and protein Nrf2, NQO1, HO-1 and SOD-1 were significantly increased (P < 0.05) in the ischemia-reperfusion period compared with the ischemic period. In the control group, the levels of mRNA and protein of Nrf2, NQO1, HO-1 and SOD-1 were significantly decreased (P < 0.05) in the ischemia-reperfusion period compared with the ischemic period. Compared with the ischemic period, the ischemia-reperfusion phase showed significantly increased SOD activity and significantly decreased MDA content in the hydrogen-rich water group, while SOD activity was significantly decreased, and MDA content was significantly increased in the control group (P < 0.05). Hydrogen-rich water can activate the Nrf2/ARE signaling pathway, alleviate ischemia-reperfusion injury in isolated rat hearts and reduce the oxidative stress level of myocardial tissue.

    更新日期:2019-11-26
  • Differential expression of recently duplicated PTOX genes in Glycine max during plant development and stress conditions
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-09-11
    Rachel Alves Maia, Kátia Daniella da Cruz Saraiva, André Luiz Maia Roque, Karine Leitão Lima Thiers, Clesivan Pereira dos Santos, João Hermínio Martins da Silva, Daniel Ferreira Feijó, Birgit Arnholdt-Schmitt, José Hélio Costa

    Plastid terminal oxidase (PTOX) is a chloroplast enzyme that catalyzes oxidation of plastoquinol (PQH2) and reduction of molecular oxygen to water. Its function has been associated with carotenoid biosynthesis, chlororespiration and environmental stress responses in plants. In the majority of plant species, a single gene encodes the protein and little is known about events of PTOX gene duplication and their implication to plant metabolism. Previously, two putative PTOX (PTOX1 and 2) genes were identified in Glycine max, but the evolutionary origin and the specific function of each gene was not explored. Phylogenetic analyses revealed that this gene duplication occurred apparently during speciation involving the Glycine genus ancestor, an event absent in all other available plant leguminous genomes. Gene expression evaluated by RT-qPCR and RNA-seq data revealed that both PTOX genes are ubiquitously expressed in G. max tissues, but their mRNA levels varied during development and stress conditions. In development, PTOX1 was predominant in young tissues, while PTOX2 was more expressed in aged tissues. Under stress conditions, the PTOX transcripts varied according to stress severity, i.e., PTOX1 mRNA was prevalent under mild or moderate stresses while PTOX2 was predominant in drastic stresses. Despite the high identity between proteins (97%), molecular docking revealed that PTOX1 has higher affinity to substrate plastoquinol than PTOX2. Overall, our results indicate a functional relevance of this gene duplication in G. max metabolism, whereas PTOX1 could be associated with chloroplast effectiveness and PTOX2 to senescence and/or apoptosis.

    更新日期:2019-11-04
  • Current understanding of structure, function and biogenesis of yeast mitochondrial ATP synthase
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-08-16
    I. Made Artika

    The yeast mitochondrial ATP synthase is a rotary molecular machine primarily responsible for the production of energy used to drive cellular processes. The enzyme complex is composed of 17 different subunits grouped into a soluble F1 sector and a membrane-embedded F0 sector. The catalytic head of the F1 sector and the membrane integrated motor module in the F0 sector are connected by two stalks, the F1 central stalk and the F0 peripheral stalk. Proton translocation through the F0 motor module drives the rotation of the subunit 910-ring that generates torque which is transmitted to the calaytic head through the γ subunit of the central stalk. The rotation of the γ subunit causes changes in conformation of the catalytic head which leads to the synthesis of ATP. Biogenesis of the enzyme involves modular assembly of polypeptides of dual genetic origin, the nuclear and the mitochondrial genomes. Most of the yeast ATP synthase subunits are encoded by the genome of the nucleus, translated on cytosolic ribosomes and imported into mitochondria. In the mitochondria, the enzyme forms a dimer which contributes to the formation of cristae, a characteristic of mitochondrial morphology. Substantial progress has recently been made on the elucidation of detailed stucture, function and biogenesis of yeast mitochondrial ATP synthase. The recent availability of high-resolution structure of the complete monomeric form, as well as the atomic model for the dimeric F0 sector, has advanced the understanding of the enzyme complex. This review is intended to provide an overview of current understanding of the molecular structure, catalytic mechanism, subunit import into mitochondria, and the subunit assembly into the enzyme complex. This is important as the yeast mitochondrial ATP synthase may be used as a model for understanding the corresponding enzyme complexes from human and other eukaryotic cells in physiological and diseased states.

    更新日期:2019-11-04
  • Increased reactive oxygen species production and maintenance of membrane potential in VDAC-less Neurospora crassa mitochondria
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-08-07
    Sabbir R. Shuvo, Lilian M. Wiens, Saravananaidu Subramaniam, Jason R. Treberg, Deborah A. Court

    The highly abundant voltage-dependent anion-selective channel (VDAC) allows transit of metabolites across the mitochondrial outer membrane. Previous studies in Neurospora crassa showed that the LoPo strain, expressing 50% of normal VDAC levels, is indistinguishable from wild-type (WT). In contrast, the absence of VDAC (ΔPor-1), or the expression of an N-terminally truncated variant VDAC (ΔN2-12porin), is associated with deficiencies in cytochromes b and aa3 of complexes III and IV and concomitantly increased alternative oxidase (AOX) activity. These observations led us to investigate complex I and complex II activities in these strains, and to explore their mitochondrial bioenergetics. The current study reveals that the total NADH dehydrogenase activity is similar in mitochondria from WT, LoPo, ΔPor-1 and ΔN2-12porin strains; however, in ΔPor-1 most of this activity is the product of rotenone-insensitive alternative NADH dehydrogenases. Unexpectedly, LoPo mitochondria have increased complex II activity. In all mitochondrial types analyzed, oxygen consumption is higher in the presence of the complex II substrate succinate, than with the NADH-linked (complex I) substrates glutamate and malate. When driven by a combination of complex I and II substrates, membrane potentials (Δψ) and oxygen consumption rates (OCR) under non-phosphorylating conditions are similar in all mitochondria. However, as expected, the induction of state 3 (phosphorylating) conditions in ΔPor-1 mitochondria is associated with smaller but significant increases in OCR and smaller decreases in Δψ than those seen in wild-type mitochondria. High ROS production, particularly in the presence of rotenone, was observed under non-phosphorylating conditions in the ΔPor-1 mitochondria. Thus, the absence of VDAC is associated with increased ROS production, in spite of AOX activity and wild-type OCR in ΔPor-1 mitochondria.

    更新日期:2019-11-04
  • Protection from ionizing radiation-induced genotoxicity and apoptosis in rat bone marrow cells by HESA-A: a new herbal-marine compound
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-08-06
    Maryam Hazbavi, Mansoureh Zarei, Roghayeh Nazaralivand, Hojattollah Shahbazian, Mohsen Cheki

    HESA-A is an herbal-marine compound which improves the quality of life of end-stage cancer patients. The aim of the present study was to evaluate the possible protective effect of HESA-A against IR-induced genotoxicity and apoptosis in rat bone marrow. Rats were given HESA-A orally at doses of 150 and 300 mg/kg body weight for seven consecutive days. On the seventh day, the rats were irradiated with 4 Gy X-rays at 1 h after the last oral administration. The micronucleus assay, reactive oxygen species (ROS) level analysis, hematological analysis and flow cytometry were used to assess radiation antagonistic potential of HESA-A. Administration of 150 and 300 mg/kg of HESA-A to irradiated rats significantly reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs), and also increased PCE/(PCE + NCE) ratio in bone marrow cells. Moreover, pretreatment of irradiated rats with HESA-A (150 and 300 mg/kg) significantly decreased ROS level and apoptosis in bone marrow cells, and also increased white blood cells count in peripheral blood. For the first time in this study, it was observed that HESA-A can have protective effects against radiation-induced genotoxicity and apoptosis in bone marrow cells. Therefore, HESA-A can be considered as a candidate for future studies to reduce the side effects induced by radiotherapy in cancer patients.

    更新日期:2019-11-04
  • Correction to: The synergistic effect of mefenamic acid with ionizing radiation in colon cancer
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-06-25
    Seyed Jalal Hosseinimehr, Zahar Safavi, Sahar Kangarani Farahani, Zohreh Noaparast, Arash Ghasemi, Hossein Asgarian-Omran

    The original version of this article unfortunately contained a mistake. The name of “Zohreh Noaparast” is now corrected in the author group of this article.

    更新日期:2019-11-04
  • Retraction Note to: Acridine yellow. A novel use to estimate and measure the plasma membrane potential in Saccharomyces cerevisiae
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-05-31
    Martha Calahorra, Norma Silvia Sánchez, Antonio Peña

    The authors have retracted this article [1]. After publication the dye used in this study was analysed by NMR and mass spectroscopy and found not to be acridine yellow, but rather, was identified as thioflavin T.

    更新日期:2019-11-04
  • MicroRNA-141 protects PC12 cells against hypoxia/reoxygenation-induced injury via regulating Keap1-Nrf2 signaling pathway
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-07-04
    Bin Zhou, Hong-Yun Liu, Bao-Lian Zhu, Ai-Xia Yue

    To understand the role of microRNA-141 (miR-141) in hypoxia/reoxygenation (H/R)-induced PC12 cell injury via modulation of Keap1/Nrf2 signaling pathway. PC12 cells were divided into Control, H/R, H/R + miR-141 mimics, H/R + NC, H/R + miR-141 inhibitor, H/R + siKeap1 and H/R + miR-141 inhibitors+siKeap1 groups. The expression of miR-141 and Keap1/Nrf2 pathway was measured by qRT-PCR and western blotting, cell viability evaluated by MTT assay while cell apoptosis tested by flow cytometry. Besides, MDA (malondialdehyde), SOD (Super Oxide Dismutase) and LDH (lactate dehydrogenase) levels were determined. DCFH-DA and JC-1 staining were used to measure ROS and mitochondrial membrane potential (MMP) respectively. Compared with Controls, PC12 cells induced by H/R exhibited decreased cell viability and increased cell apoptosis rate, with elevated MDA, LDH and ROS and reduced SOD levels; and meanwhile, MMP and miR-141 expression were declined, whereas cytoplasmic Nrf2 levels were enhanced with the downregulated nuclear Nrf2 level (all P < 0.05). However, these cells treated with miR-141 mimics and siKeap1 showed obvious improvement in H/R-induced cell injury, while miR-141 inhibitors presented significantly aggravated cell injury (both P < 0.05). Besides, siKeap1 can reverse the effect of miRNA-141 inhibitors on aggravating H/R-induced PC12 cell injury. miR-141-mediated Keap1/Nrf2 signaling pathway to promote cell viability, inhibit cell apoptosis and reduce oxidative stress of PC12 cells, thereby alleviating H/R-induced cell injury.

    更新日期:2019-11-04
  • Arylboronic acids inhibit P2X7 receptor function and the acute inflammatory response
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-06-29
    Robson Xavier Faria, Noemi de Jesus Hiller, Juliana Pimenta Salles, Jackson Antonio Lamounier Camargos Resende, Roberta Tosta Diogo, Natalia Lidmar von Ranke, Murilo Lamim Bello, Carlos Rangel Rodrigues, Helena Carla Castro, Daniela de Luna Martins

    The P2X7 receptor (P2X7R) is an ion channel which is activated by interactions with the extracellular ATP molecules. The molecular complex P2X7R/ATP induces conformational changes in the protein subunits, opening a pore in the ion channel macromolecular structure. Currently, the P2X7R has been studied as a potential therapeutic target of anti-inflammatory drugs. Based on this, a series of eight boronic acids (NO) analogs were evaluated on the biologic effect of this pharmacophoric group on the human and murine P2X7R. The boronic acids derivatives NO-01 and NO-12 inhibited in vitro human and murine P2X7R function. These analogs compounds showed effect better than compound BBG and similar to inhibitor A740003 for inhibiting dye uptake, in vitro IL-1β release and ATP-induced paw edema in vivo. In both, in vitro and in vivo assays the compound NO-01 showed to be the hit compound in the present series of the arylboronic acids analogs. The molecular docking suggests that the NO derivatives bind into the upper body domain of the P2X7 pore and that the main intermolecular interaction with the two most active NO derivatives occur with the residues Phe 95, 103 and 293 by hydrophobic interactions and with Leu97, Gln98 and Ser101 by hydrogen bonds.. These results indicate that the boronic acid derivative NO-01 shows the lead compound characteristics to be used as a scaffold structure to the development of new P2X7R inhibitors with anti-inflammatory action.

    更新日期:2019-11-04
  • Mitochondria as a possible target for nicotine action
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-06-13
    Dominika Malińska, Mariusz R. Więckowski, Bernadeta Michalska, Karolina Drabik, Monika Prill, Paulina Patalas-Krawczyk, Jarosław Walczak, Jędrzej Szymański, Carole Mathis, Marco Van der Toorn, Karsta Luettich, Julia Hoeng, Manuel C. Peitsch, Jerzy Duszyński, Joanna Szczepanowska

    Mitochondria are multifunctional and dynamic organelles deeply integrated into cellular physiology and metabolism. Disturbances in mitochondrial function are involved in several disorders such as neurodegeneration, cardiovascular diseases, metabolic diseases, and also in the aging process. Nicotine is a natural alkaloid present in the tobacco plant which has been well studied as a constituent of cigarette smoke. It has also been reported to influence mitochondrial function both in vitro and in vivo. This review presents a comprehensive overview of the present knowledge of nicotine action on mitochondrial function. Observed effects of nicotine exposure on the mitochondrial respiratory chain, oxidative stress, calcium homeostasis, mitochondrial dynamics, biogenesis, and mitophagy are discussed, considering the context of the experimental design. The potential action of nicotine on cellular adaptation and cell survival is also examined through its interaction with mitochondria. Although a large number of studies have demonstrated the impact of nicotine on various mitochondrial activities, elucidating its mechanism of action requires further investigation.

    更新日期:2019-11-04
  • Hyperthermia potentiates cisplatin cytotoxicity and negative effects on mitochondrial functions in OVCAR-3 cells
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-07-22
    Arturas Sukovas, Giedre Silkuniene, Sonata Trumbeckaite, Aldona Jasukaitiene, Laima Degutyte-Fomins, Vida Mildaziene, Antanas Gulbinas, Rasa Baniene, Zilvinas Dambrauskas, Saulius Paskauskas

    The aim of this study was to determine the effects of hyperthermia, cisplatin and their combination on mitochondrial functions such as glutamate dehydrogenase (GDH) activity and mitochondrial respiration rates, as well as survival of cultured ovarian adenocarcinoma OVCAR-3 cells. Cells treated for 1 h with hyperthermia (40 and 43 °C) or cisplatin (IC50) or a combination of both treatments were left for recovery at 37 °C temperature for 24 h or 48 h. The obtained results revealed that 43 °C hyperthermia potentiated effects of cisplatin treatment: combinatory treatment more strongly suppressed GDH activity and expression, mitochondrial functions, and decreased survival of OVCAR-3 cells in comparison to separate single treatments. We obtained evidence that in the OVCAR-3 cell line GDH was directly activated by hyperthermia (cisplatin eliminated this effect); however, this effect was followed by GDH inhibition after 48 h recovery. A combination of 43 °C hyperthermia with cisplatin induced stronger GDH inhibition in comparison to separate treatments, and negative effects exerted on GDH activity correlated with suppression of mitochondrial respiration with glutamate + malate. Cisplatin did not induce uncoupling of oxidative phosphorylation in OVCAR-3 cells but induced impairment of the outer mitochondrial membrane in combination with 43 °C hyperthermia. Hyperthermia (43 °C) potentiated cytotoxicity of cisplatin in an OVCAR-3 cell line.

    更新日期:2019-11-04
  • Effect of hypoxia on mitochondrial enzymes and ultrastructure in the brain cortex of rats with different tolerance to oxygen shortage
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-07-24
    Galina D. Mironova, Lubov L. Pavlik, Yulia I. Kirova, Natalia V. Belosludtseva, Alexey A. Mosentsov, Natalya V. Khmil, Elita L. Germanova, Ludmila D. Lukyanova

    The mitochondrial structure and the contents of subunits (NDUFV2, SDHA, Cyt b, COX1) of mitochondrial respiratory complexes I–IV as well as of the hypoxia-inducible factor (HIF-1α) in the brain cortex (BC) of rats with high resistance (HR) and low resistance (LR) to hypoxia were studied for the first time depending on the severity of hypoxia. Different regimes of 30-min hypobaric hypoxia (pO2 14, 10, and 8%) were used. It was found that cortical mitochondria responded to 30-min hypobaric hypoxia of different severity with typical and progressing changes in mitochondrial structure and function of mitochondrial enzymes. Under 14 and 10% hypoxia, animals developed compensatory structural and metabolic responses aimed at supporting the cell energy homeostasis. Consequently, these hypoxia regimes can be used for treatment in pressure chambers. At the same time, decreasing the oxygen concentration in the inhaled air to 8% led to the appearance of destructive processes in brain mitochondria. The features of mitochondrial ultrastructure and the function of respiratory enzymes in the BC of HR and LR rats exposed to normoxic and hypoxic conditions suggest that the two types of animals had two essentially distinct functional and metabolic patterns determined by different efficiency of the energy apparatus. The development of adaptive and destructive responses involved different metabolic pathways of the oxidation of energy substrates and different efficiency of the functioning of mitochondrial respiratory carriers.

    更新日期:2019-11-04
  • Effect of hypothermia on the functional activity of liver mitochondria of grass snake ( Natrix natrix ): inhibition of succinate-fueled respiration and K + transport, ROS-induced activation of mitochondrial permeability transition
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-04-13
    Mikhail V. Dubinin, Anton O. Svinin, Aleksander A. Vedernikov, Vlada S. Starinets, Kirill S. Tenkov, Konstantin N. Belosludtsev, Victor N. Samartsev

    The article considers the comparative analysis of the functional activity of mitochondria isolated from the liver of grass snakes, Natrix natrix (Linnaeus, 1758) that were kept at different temperatures (23–26 °C and 4-5 °C). It was found that liver mitochondria of hypothermia-exposed grass snakes are characterized by weak coupling of oxidative phosphorylation as compared to mitochondria of active animals which is caused by inhibition of succinate-fuelled respiration in ADP-stimulated state, as well as by activation of basal non-phosphorylating rate. Inhibition of mitochondrial respiration in hibernating animals is associated with a decrease in the activity of the respiratory chain complexes of organelles. A significant decrease in the rate of K+ transport in the liver mitochondria of hibernating animals has been established. Under these conditions, a decrease in the calcium capacity of the organelles was also revealed, which indicates a decrease in the resistance of the mitochondria of hibernating animals to the induction of the Ca2+-dependent mitochondrial pore. All these changes in the functional activity of mitochondria are observed on the background of increasing H2O2 production as well as increasing the proportion of polyunsaturated fatty acids in phospholipid composition of mitochondrial membranes, which are the targets of reactive oxygen species. It can lead to increased formation of lipid peroxides and activation of destructive processes associated with the induction of Ca2+-dependent mitochondrial pore.

    更新日期:2019-11-04
  • Bishonokiol A inhibits breast cancer cell invasion and migration by suppressing hypoxia inducible factor-1α
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-05-06
    Hong-Mei Li, Jian Miao, Meilin Zhu, Meijia Gao, Yiqun Dai, Qiang Huo, Tao Ma, Cheng-Zhu Wu

    Hypoxia inducible factor-1α (HIF-1α) plays a central role in cell survival, invasion, metastasis and angiogenesis, and also is emerging as an important target in anti-cancer drug discovery. In the present study, bishonokiol A, a dimeric neolignan isolated from Magnolia grandiflora, was identified as a novel HIF-1α inhibitor. We here demonstrated that in a dose-dependent manner, bishonokiol A inhibited metastasis-related cell invasion and migration of cobalt chloride (CoCl2)-induced MCF-7 and MDA-MB-231 cells, associating with the reduction in HIF-1α levels. Transfection of MDA-MB-231 cells with HIF-1α small interfering ribonucleic acid (siRNA) resulted in a reduction in cell invasion and migration. Furthermore, we found that bishonokiol A not only inhibited the synthesis of HIF-1α protein and protein kinase B (AKT-473) phosphorylation without affecting the expression of HIF-1α mRNA or ubiquitination degradation, but also inhibited the expression of matrix metalloproteinase-9 (MMP-9) and promoter activity. Nude mice bearing MDA-MB-231 cells incubation were treated with bishonokiol A and results showed that bishonokiol A exhibited potent antitumor activity and low toxicity. Therefore, we suggest that bishonokiol A may be a potential inhibitor of HIF-1α and effective antitumor agent for breast cancer.

    更新日期:2019-11-04
  • Preconditioning the rat heart with sodium thiosulfate preserved the mitochondria in response to ischemia-reperfusion injury
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-03-30
    Sriram Ravindran, Gino A. Kurian

    Sodium thiosulfate preconditioning (SIPC) was recently reported to be cardioprotective due to its ability to inhibit caspase-3 activation, chelate calcium ions and scavenge free radicals. However, the rationale behind its ability to improve the contractility of isolated rat heart challenged with ischemia-reperfusion injury (IR) is not well understood. As mitochondrial preservation is implicated in cardioprotection against IR, the present study was conceived to identify whether the cardioprotective effects of SIPC is associated with mitochondrial preservation. Using the isolated Langendorff rat heart model, 1 mM sodium thiosulfate (STS) was used to precondition the rat heart before IR and was used to study its effect on cardiac mitochondria. The IR heart experienced a ventricular contractile dysfunction that was improved by SIPC. Upon assessing in-gel the ATP synthetic capacity of mitochondria from IR heart, there was a significant decline, while in SIPC it was well preserved close to sham. As a sustained flow of electrons through the ETC and well-integrated mitochondria are the prerequisites for ATP synthesis, SIPC improved the activities of ETC complex enzymes (I-IV), which was reflected from the preserved ultrastructure of the mitochondria as analyzed from electron-microscopy in the treated rat hearts. This observation was coherent with the elevated expression of PGC1α (20%), a critical regulator of ATP production, which increased the mitochondrial copy number as well in the STS treated heart compared to IR. In conclusion, mitochondria might be a critical target for SIPC mediated cardioprotection against IR.

    更新日期:2019-11-04
  • The synergistic effect of mefenamic acid with ionizing radiation in colon cancer
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-03-07
    Seyed Jalal Hosseinimehr, Zahar Safavi, Sahar Kangarani Farahani, Zohreh Noaparst, Arash Ghasemi, Hossein Asgarian-Omran

    Despite radiotherapy is an effective regimen in cancer treatment, resistance to tumor therapy still is a major challenge to radiotherapy and results in cancer recurrence and metastasis. Then the sensitization of tumor cells to ionizing radiation (IR) would be beneficial in cancer treatment. The aim of this study was to evaluate the synergistic effect of mefenamic acid (MEF) on colon cancer cell (HT-29) exposure to IR. HT-29 cells were treated with MEF and then exposed to IR. The synergistic effect of MEF is evaluated by clonogenic assay and flow cytometry. The productions of reactive oxygen species (ROS) were determined in irradiated and treated cells with MEF. The findings of this study showed that MEF had anti-cancer effect on colon cancer cell line and it increased the apoptosis in irradiated HT-29 cells. Also MEF reduced the number of cell colonies when HT-29 cells pre-treated with MEF and irradiated. MEF increased ROS production in irradiated cells. This additive effect of MEF with IR in killing of HT-29 cell was observed at low (10 μM) and medium (100 μM) concentrations of MEF. The present study demonstrates that MEF to be an additive effect on apoptosis and cell death induced by IR in colon cancer cells.

    更新日期:2019-11-04
  • Modulation of glucose-related metabolic pathways controls glucose level in airway surface liquid and fight oxidative stress in cystic fibrosis cells
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-04-27
    M. Favia, L. de Bari, R. Lassandro, Anna Atlante

    Direct and indirect evidences show that elevated glucose concentrations in airway surface liquid (ASL) promote lung infection by pathogens, playing a role in the progression of the Cystic Fibrosis (CF) disease. The joint action of transporter/s for glucose and of the cellular enzymes is essential in order to try to lower ASL glucose level. Inside the cell, the glycolysis and the pentose phosphate pathway (PPP) compete for the utilization of glucose-6-phosphate (G6P), the product in which glucose, after entry within the cell and phosphorylation, is trapped. The study aims to clarify whether, modulating the activity of enzymatic proteins and/or the level of metabolites/cofactors, involved in intracellular glucose utilization, a lowering of the extracellular glucose level in CF occurs. Biochemical approaches have enabled us to understand i) how G6P is shunted between glycolysis and PPP and ii) that mitochondria, more than enzymes/cofactors participating to the two cell glucose utilization pathways, are protagonists of the scene in counteracting the high ASL glucose level as well as oxidative stress in CF.

    更新日期:2019-11-04
  • Role of DJ-1 in the mechanism of pathogenesis of Parkinson's disease
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-05-03
    Ludmila P. Dolgacheva, Alexey V. Berezhnov, Evgeniya I. Fedotova, Valery P. Zinchenko, Andrey Y. Abramov

    DJ-1 protein has multiple specific mechanisms to protect dopaminergic neurons against neurodegeneration in Parkinson's disease. Wild type DJ-1 can acts as oxidative stress sensor and as an antioxidant. DJ-1 exhibits the properties of molecular chaperone, protease, glyoxalase, transcriptional regulator that protects mitochondria from oxidative stress. DJ-1 increases the expression of two mitochondrial uncoupling proteins (UCP 4 and UCP5), that decrease mitochondrial membrane potential and leads to the suppression of ROS production, optimizes of a number of mitochondrial functions, and is regarded as protection for the neuronal cell survival. We discuss also the stabilizing interaction of DJ-1 with the mitochondrial Bcl-xL protein, which regulates the activity of (Inositol trisphosphate receptor) IP3R, prevents the cytochrome c release from mitochondria and inhibits the apoptosis activation. Upon oxidative stress DJ-1 is able to regulate various transcription factors including nuclear factor Nrf2, PI3K/PKB, and p53 signal pathways. Stress-activated transcription factor Nrf2 regulates the pathways to protect cells against oxidative stress and metabolic pathways initiating the NADPH and ATP production. DJ-1 induces the Nrf2 dissociation from its inhibitor Keap1 (Kelch-like ECH-associated protein 1), promoting Nrf2 nuclear translocation and binding to antioxidant response elements. DJ-1 is shown to be a co-activator of the transcription factor NF-kB. Under nitrosative stress, DJ-1 may regulate PI3K/PKB signaling through PTEN transnitrosylation, which leads to inhibition of phosphatase activity. DJ-1 has a complex modulating effect on the p53 pathway: one side DJ-1 directly binds to p53 to restore its transcriptional activity and on the other hand DJ-1 can stimulate deacylation and suppress p53 transcriptional activity. The ability of the DJ-1 to induce activation of different transcriptional factors and change redox balance protect neurons against aggregation of α-synuclein and oligomer-induced neurodegeneration.

    更新日期:2019-11-04
  • Ropivacaine inhibits tumor angiogenesis via sodium-channel-independent mitochondrial dysfunction and oxidative stress
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-03-07
    Jingwen Yang, Guangting Li, Kaibei Bao, Weihua Liu, Yaozhi Zhang, Weijen Ting

    The anti-cancer role of local anesthetics has garnered attention in recent years because increasing evidence show that local anesthetics reduce the risk of tumor metastasis and recurrence. Angiogenesis, the formation of new blood vessels, is fundamental for tumor growth and metastasis. The role of local anesthetics on tumor angiogenesis still remains unknown. Using human lung tumor-associated endothelial cell (HLT-EC) and angiogenesis models, our work shows that ropivacaine at the clinically relevant concentration is active against multiple biological functions of HLT-EC but not lung tumor cells. Ropivacaine inhibits HLT-EC capillary network formation, growth and survival. The anti-angiogenic activity of ropivacaine is further confirmed in in vivo angiogenesis mouse model. Mechanistically, we show that ropivacaine inhibits HLT-EC mitochondrial respiration via specifically targeting mitochondrial respiratory complex II. As a consequence of mitochondrial respiration inhibition, we observe the energy depletion, oxidative stress and damage in HLT-EC after ropivacaine exposure. Additionally, an antioxidant agent completely reverses the inhibitory effects of ropivacaine, suggesting that oxidative stress is required for the action of ropivacaine in HLT-EC. Interestingly, mitochondrial dysfunction and oxidative stress induced by ropivacaine is sodium channel-independent. Our work demonstrates the potent inhibitory effects of ropivacaine in lung tumor angiogenesis by inducing mitochondrial dysfunction. These findings provide significant insight into the potential mechanisms by which local anaesthetics may negatively affect tumor reoccurrence and metastasis.

    更新日期:2019-11-04
  • Polymorphisms in plastoquinol oxidase (PTOX) from Arabidopsis accessions indicate SNP-induced structural variants associated with altitude and rainfall
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-01-07
    Karine Leitão Lima Thiers, João Hermínio Martins da Silva, Geraldo Rodrigues Sartori, Clesivan Pereira dos Santos, Kátia Daniella da Cruz Saraiva, André Luiz Maia Roque, Birgit Arnholdt-Schmitt, José Hélio Costa

    Plant plastoquinol oxidase (PTOX) is a chloroplast oxidoreductase involved in carotenoid biosynthesis, chlororespiration, and response to environmental stresses. The present study aimed to gain insight of the potential role of nucleotide/amino acid changes linked to environmental adaptation in PTOX gene/protein from Arabidopsis thaliana accessions. SNPs in the single-copy PTOX gene were identified in 1190 accessions of Arabidopsis using the Columbia-0 PTOX as a reference. The identified SNPs were correlated with geographical distribution of the accessions according to altitude, climate, and rainfall. Among the 32 identified SNPs in the coding region of the PTOX gene, 16 of these were characterized as non-synonymous SNPs (in which an AA is altered). A higher incidence of AA changes occurred in the mature protein at positions 78 (31%), 81 (31.4%), and 323 (49.9%). Three-dimensional structure prediction indicated that the AA change at position 323 (D323N) leads to a PTOX structure with the most favorable interaction with the substrate plastoquinol, when compared with the reference PTOX structure (Columbia-0). Molecular docking analysis suggested that the most favorable D323N PTOX-plastoquinol interaction is due to a better enzyme-substrate binding affinity. The molecular dynamics revealed that plastoquinol should be more stable in complex with D323N PTOX, likely due a restraint mechanism in this structure that stabilize plastoquinol inside of the reaction center. The integrated analysis made from accession geographical distribution and PTOX SNPs indicated that AA changes in PTOX are related to altitude and rainfall, potentially due to an adaptive positive environmental selection.

    更新日期:2019-11-04
  • Hydrophobicity, rather than secondary structure, is essential for the SRP dependent targeting of GPR35 to the ER membrane
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-01-31
    Jon K. Cherry, Cheryl A. Woolhead

    The folding and targeting of hydrophobic transmembrane domains poses a major challenge to the cell. Several membrane proteins have been shown to gain some degree of secondary structure within the ribosome tunnel and to retain this conformation throughout maturation. However, there is little information on one of the largest classes of eukaryotic membrane proteins; the G protein-coupled receptors (GPCRs). In this study we show that the signal anchor domain of GPR35 remains in an extended conformation whilst exiting the ribosome tunnel, the polypeptide chain then forms interactions with components of the SRP targeting pathway, and the Sec61 translocon, resulting in a compacted conformation prior to integration into the ER membrane. We conclude that transmembrane structure is most likely adopted after the domain leaves the ribosome tunnel and that the interaction of the signal anchor with SRP is dependent on the native levels of hydrophobicity within the first transmembrane domain. Therefore, we propose a mechanism by which the first transmembrane domains of multi-spanning membrane proteins adopt compacted structures following SRP targeting but before insertion into the ER membrane.

    更新日期:2019-11-04
  • New use for CETSA: monitoring innate immune receptor stability via post-translational modification by OGT.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2018-04-20
    Walter R Drake,Ching-Wen Hou,Natasha E Zachara,Catherine Leimkuhler Grimes

    O-GlcNAcylation is a dynamic and functionally diverse post-translational modification shown to affect thousands of proteins, including the innate immune receptor nucleotide-binding oligomerization domain-containing protein 2 (Nod2). Mutations of Nod2 (R702W, G908R and 1007 fs) are associated with Crohn's disease and have lower stabilities compared to wild type. Cycloheximide (CHX)-chase half-life assays have been used to show that O-GlcNAcylation increases the stability and response of both wild type and Crohn's variant Nod2, R702W. A more rapid method to assess stability afforded by post-translational modifications is necessary to fully comprehend the correlation between NLR stability and O-GlcNAcylation. Here, a recently developed cellular thermal shift assay (CETSA) that is typically used to demonstrate protein-ligand binding was adapted to detect shifts in protein stabilization upon increasing O-GlcNAcylation levels in Nod2. This assay was used as a method to predict if other Crohn's associated Nod2 variants were O-GlcNAcylated, and also identified the modification on another NLR, Nod1. Classical immunoprecipitations and NF-κB transcriptional assays were used to confirm the presence and effect of this modification on these proteins. The results presented here demonstrate that CETSA is a convenient method that can be used to detect the stability effect of O-GlcNAcylation on O-GlcNAc-transferase (OGT) client proteins and will be a powerful tool in studying post-translational modification.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Strength in diversity: functional diversity among olfactory neurons of the same type.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-01-04
    Eryn Slankster,Seth R Odell,Dennis Mathew

    Most animals depend upon olfaction to find food, mates, and to avoid predators. An animal's olfactory circuit helps it sense its olfactory environment and generate critical behavioral responses. The general architecture of the olfactory circuit, which is conserved across species, is made up of a few different neuronal types including first-order receptor neurons, second- and third-order neurons, and local interneurons. Each neuronal type differs in their morphology, physiology, and neurochemistry. However, several recent studies have suggested that there is intrinsic diversity even among neurons of the same type and that this diversity is important for neural function. In this review, we first examine instances of intrinsic diversity observed among individual types of olfactory neurons. Next, we review potential genetic and experience-based plasticity mechanisms that underlie this diversity. Finally, we consider the implications of intrinsic neuronal diversity for circuit function. Overall, we hope to highlight the importance of intrinsic diversity as a previously underestimated property of circuit function.

    更新日期:2019-11-01
  • Neural plasticity in developing and adult olfactory pathways - focus on the human olfactory bulb.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2019-01-04
    C Huart,Ph Rombaux,T Hummel

    The topic of human adult neural plasticity and neurogenesis is of great interest for medical and scientific community, but it is also largely debated. In the last years, an increasing interest has been paid to the olfactory system, and particularly to the plasticity of the olfactory bulb (OB). While the molecular/cellular mechanisms underlying OB plasticity remain a matter of debate, measurements of the OB using magnetic resonance imaging clearly indicate that it is a highly plastic structure. In this review, we present results regarding the plasticity of the human adult olfactory system.

    更新日期:2019-11-01
  • Forever young: Neoteny, neurogenesis and a critique of critical periods in olfaction.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2018-11-14
    David M Coppola,Leonard E White

    The critical period concept has been one of the most transcendent in science, education, and society forming the basis of our fixation on 'quality' of childhood experiences. The neural basis of this process has been revealed in developmental studies of visual, auditory and somatosensory maps and their enduring modification through manipulations of experience early in life. Olfaction, too, possesses a number of phenomena that share key characteristics with classical critical periods like sensitive temporal windows and experience dependence. In this review, we analyze the candidate critical period-like phenomena in olfaction and find them disanalogous to classical critical periods in other sensory systems in several important ways. This leads us to speculate as to why olfaction may be alone among exteroceptive systems in lacking classical critical periods and how life-long neurogenesis of olfactory sensory neurons and bulbar interneurons-a neotenic vestige-- relates to the structure and function of the mammalian olfactory system.

    更新日期:2019-11-01
  • Low survival rate of young adult-born olfactory sensory neurons in the undamaged mouse olfactory epithelium.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2018-10-12
    Sajishnu P Savya,Tenzin Kunkhyen,Claire E J Cheetham

    Olfactory sensory neurons (OSNs) are generated throughout life from progenitor cells in the olfactory epithelium. OSN axons project in an odorant receptor-specific manner to the olfactory bulb (OB), forming an ordered array of glomeruli where they provide sensory input to OB neurons. The tetracycline transactivator (tTA) system permits developmental stage-specific expression of reporter genes in OSNs and has been widely used for structural and functional studies of the development and plasticity of the mouse olfactory system. However, the cellular ages at which OSNs stop expressing reporters driven by the immature OSN-specific Gγ8-tTA driver line and begin to express reporters driven by the mature OSN-specific OMP-tTA driver line have not been directly determined. We pulse-labeled terminally dividing cells in the olfactory epithelium of 28-day-old (P28) mice with EdU and analyzed EdU labeling in OSNs expressing fluorescent reporter proteins under control of either the Gγ8-tTA or OMP-tTA driver line 5-14 days later. Expression of OMP-tTA-driven reporters began in 6-day-old OSNs, while the vast majority of newborn OSNs did not express Gγ8-tTA-driven fluorescent proteins beyond 8 days of cellular age. Surprisingly, we also found a low survival rate for P28-born OSNs, very few of which survived for more than 14 days. We propose that OSN survival requires the formation of stable synaptic connections and hence may be dependent on organismal age.

    更新日期:2019-11-01
  • Deafferentation-induced alterations in mitral cell dendritic morphology in the adult zebrafish olfactory bulb.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2018-09-15
    Joanna M Pozzuto,Cynthia L Fuller,Christine A Byrd-Jacobs

    The removal of afferent input to the olfactory bulb by both cautery and chemical olfactory organ ablation in adult zebrafish results in a significant decrease in volume of the ipsilateral olfactory bulb. To examine the effects of deafferentation at a cellular level, primary output neurons of the olfactory bulb, the mitral cells, were investigated using retrograde tract tracing with fluorescent dextran using ex vivo brain cultures. Morphological characteristics including the number of major dendritic branches, total length of dendritic branches, area of the dendritic arbor, overall dendritic complexity, and optical density of the arbor were used to determine the effects of deafferentation on mitral cell dendrites. Following 8 weeks of permanent deafferentation there were significant reductions in the total length of dendritic branches, the area of the dendritic arbor, and the density of fine processes in the dendritic tuft. With 8 weeks of chronic, partial deafferentation there were significant reductions in all parameters examined, including a modified Sholl analysis that showed significant decreases in overall dendritic complexity. These results show the plasticity of mitral cell dendritic structures in the adult brain and provide information about the response of these output neurons following the loss of sensory input in this key model system.

    更新日期:2019-11-01
  • Loss of odor-induced c-Fos expression of juxtaglomerular activity following maintenance of mice on fatty diets.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2018-09-12
    Erminia Fardone,Arda B Celen,Nicholas A Schreiter,Nicolas Thiebaud,Melissa L Cooper,Debra Ann Fadool

    Diet-induced obesity (DIO) decreases the number of OMP+ olfactory sensory neurons (OSN) in the olfactory epithelium by 25% and reduces correlate axonal projections to the olfactory bulb (OB). Whether surviving OSNs have equivalent odor responsivity is largely unknown. Herein, we utilized c-fos immediate-early gene expression to map neuronal activity and determine whether mice weaned to control (CF), moderately-high fat (MHF), or high-fat (HF) diet for a period of 6 months had changes in odor activation. Diet-challenged M72-IRES-tau-GFP mice were exposed to either a preferred M72 (Olfr160) ligand, isopropyl tiglate, or clean air in a custom-made Bell-jar infusion chamber using an alternating odor exposure pattern generated by a picosprizer™. Mice maintained on fatty diets weighed significantly more and cleared glucose less efficiently as determined by an intraperitoneal glucose tolerance test (IPGTT). The number of juxtaglomerular cells (JGs) decreased following maintenance of the mice on the MHF diet for cells surrounding the medial but not lateral M72 glomerulus within a 4 cell-column distance. The percentage of c-fos + JGs surrounding the lateral M72 glomerulus decreased in fat-challenged mice whereas those surrounding the medial glomerulus were not affected by diet. Altogether, these results show an asymmetry in the responsiveness of the 'mirror image' glomerular map for the M72 receptor that shows greater sensitivity of the lateral vs. medial glomerulus upon exposure to fatty diet.

    更新日期:2019-11-01
  • Aversive learning-induced plasticity throughout the adult mammalian olfactory system: insights across development.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2018-09-02
    Jordan M Ross,Max L Fletcher

    Experiences, such as sensory learning, are known to induce plasticity in mammalian sensory systems. In recent years aversive olfactory learning-induced plasticity has been identified at all stages of the adult olfactory pathway; however, the underlying mechanisms have yet to be identified. Much of the work regarding mechanisms of olfactory associative learning comes from neonates, a time point before which the brain or olfactory system is fully developed. In addition, pups and adults often express different behavioral outcomes when subjected to the same olfactory aversive conditioning paradigm, making it difficult to directly attribute pup mechanisms of plasticity to adults. Despite the differences, there is evidence of similarities between pups and adults in terms of learning-induced changes in the olfactory system, suggesting at least some conserved mechanisms. Identifying these conserved mechanisms of plasticity would dramatically increase our understanding of how the brain is able to alter encoding and consolidation of salient olfactory information even at the earliest stages following aversive learning. The focus of this review is to systematically examine literature regarding olfactory associative learning across developmental stages and search for similarities in order to build testable hypotheses that will inform future studies of aversive learning-induced sensory plasticity in adults.

    更新日期:2019-11-01
  • The non-apoptotic action of Bcl-xL: regulating Ca(2+) signaling and bioenergetics at the ER-mitochondrion interface.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2016-05-09
    Abasha Williams,Teruo Hayashi,Daniel Wolozny,Bojiao Yin,Tzu-Chieh Su,Michael J Betenbaugh,Tsung-Ping Su

    Bcl-2 family proteins are known to competitively regulate Ca(2+); however, the specific inter-organelle signaling pathways and related cellular functions are not fully elucidated. In this study, a portion of Bcl-xL was detected at the ER-mitochondrion interface or MAM (mitochondria-associated ER membrane) in association with type 3 inositol 1,4,5-trisphosphate receptors (IP3R3); an association facilitated by the BH4 and transmembrane domains of Bcl-xL. Moreover, increasing Bcl-xL expression enhanced transient mitochondrial Ca(2+) levels upon ER Ca(2+) depletion induced by short-term, non-apoptotic incubation with thapsigargin (Tg), while concomitantly reducing cytosolic Ca(2+) release. These mitochondrial changes appear to be IP3R3-dependent and resulted in decreased NAD/NADH ratios and higher electron transport chain oxidase activity. Interestingly, extended Tg exposure stimulated ER stress, but not apoptosis, and further enhanced TCA cycling. Indeed, confocal analysis indicated that Bcl-xL translocated to the MAM and increased its interaction with IP3R3 following extended Tg treatment. Thus, the MAM is a critical cell-signaling junction whereby Bcl-xL dynamically interacts with IP3R3 to coordinate mitochondrial Ca(2+) transfer and alters cellular metabolism in order to increase the cells' bioenergetic capacity, particularly during periods of stress.

    更新日期:2019-11-01
  • Bcl-2 family in inter-organelle modulation of calcium signaling; roles in bioenergetics and cell survival.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2013-10-01
    Abasha Lewis,Teruo Hayashi,Tsung-Ping Su,Michael J Betenbaugh

    Bcl-2 family proteins, known for their apoptosis functioning at the mitochondria, have been shown to localize to other cellular compartments to mediate calcium (Ca2+) signals. Since the proper supply of Ca2+ in cells serves as an important mechanism for cellular survival and bioenergetics, we propose an integrating role for Bcl-2 family proteins in modulating Ca2+ signaling. The endoplasmic reticulum (ER) is the main Ca2+ storage for the cell and Bcl-2 family proteins competitively regulate its Ca2+ concentration. Bcl-2 family proteins also regulate the flux of Ca2+ from the ER by physically interacting with inositol 1,4,5-trisphosphate receptors (IP3Rs) to mediate their opening. Type 1 IP3Rs reside at the bulk ER to coordinate cytosolic Ca2+ signals, while type 3 IP3Rs reside at mitochondria-associated ER membrane (MAM) to facilitate mitochondrial Ca2+ uptake. In healthy cells, mitochondrial Ca2+ drives pyruvate into the citric acid (TCA) cycle to facilitate ATP production, while a continuous accumulation of Ca2+ can trigger the release of cytochrome c, thus initiating apoptosis. Since multiple organelles and Bcl-2 family proteins are involved in Ca2+ signaling, we aim to clarify the role that Bcl-2 family proteins play in facilitating Ca2+ signaling and how mitochondrial Ca2+ is relevant in both bioenergetics and apoptosis. We also explore how these insights could be useful in controlling bioenergetics in apoptosis-resistant cell lines.

    更新日期:2019-11-01
  • Mitochondrial accumulation of a lipophilic cation conjugated to an ionisable group depends on membrane potential, pH gradient and pK(a): implications for the design of mitochondrial probes and therapies.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2012-11-28
    Peter G Finichiu,Andrew M James,Lesley Larsen,Robin A J Smith,Michael P Murphy

    Mitochondria play key roles in a broad range of biomedical situations, consequently there is a need to direct bioactive compounds to mitochondria as both therapies and probes. A successful approach has been to target compounds to mitochondria by conjugation to lipophilic cations, such as triphenylphosphonium (TPP), which utilize the large mitochondrial membrane potential (Δψ(m), negative inside) to drive accumulation. This has proven effective both in vitro and in vivo for a range of bioactive compounds and probes. However so far only neutral appendages have been targeted to mitochondria in this way. Many bioactive functional moieties that we would like to send to mitochondria contain ionisable groups with pK (a) in the range that creates an assortment of charged species under physiological conditions. To see if such ionisable compounds can also be taken up by mitochondria, we determined the general requirements for the accumulation within mitochondria of a TPP cation conjugated to a carboxylic acid or an amine. Both were taken up by energised mitochondria in response to the protonmotive force. A lipophilic TPP cation attached to a carboxylic acid was accumulated to a greater extent than a simple TPP cation due to the interaction of the weakly acidic group with the pH gradient (ΔpH). In contrast, a lipophilic TPP cation attached to an amine was accumulated less than the simple cation due to exclusion of the weakly basic group by the ΔpH. From these data we derived a simple equation that describes the uptake of lipophilic cations containing ionisable groups as a function of Δψ(m), ΔpH and pK(a). These findings may facilitate the rational design of additional mitochondrial targeted probes and therapies.

    更新日期:2019-11-01
  • Uncoupling protein-1 (UCP1) contributes to the basal proton conductance of brown adipose tissue mitochondria.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2009-08-26
    Nadeene Parker,Paul G Crichton,Antonio J Vidal-Puig,Martin D Brand

    Proton leak pathways uncouple substrate oxidation from ATP synthesis in mitochondria. These pathways are classified as basal (not regulated) or inducible (activated and inhibited). Previously it was found that over half of the basal proton conductance of muscle mitochondria was catalyzed by the adenine nucleotide translocase (ANT), an abundant mitochondrial anion carrier protein. To determine whether ANT is the unique protein catalyst, or one of many proteins that catalyze basal proton conductance, we measured proton leak kinetics in mitochondria isolated from brown adipose tissue (BAT). BAT can express another mitochondrial anion carrier, UCP1, at concentrations similar to ANT. Basal proton conductance was measured under conditions where UCP1 and ANT were catalytically inactive and was found to be lower in mitochondria from UCP1 knockout mice compared to wild-type. Ablation of another abundant inner membrane protein, nicotinamide nucleotide transhydrogenase, had no effect on proton leak kinetics in mitochondria from liver, kidney or muscle, showing that basal proton conductance is not catalyzed by all membrane proteins. We identify UCP1 as a second protein propagating basal proton leak, lending support to the hypothesis that basal leak pathways are perpetrated by members of the mitochondrial anion carrier family but not by other mitochondrial inner membrane proteins.

    更新日期:2019-11-01
  • Mitochondria and reperfusion injury of the heart--a holey death but not beyond salvation.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2009-04-10
    Andrew P Halestrap

    The combination of calcium overload and oxidative stress opens a non-specific pore in the inner mitochondrial membrane known as the mitochondrial permeability transition pore (MPTP). This uncouples oxidative phosphorylation and compromises intracellular ATP levels eventually leading to necrotic cell death. In cardiac ischemia and reperfusion, as during treatment of a coronary thrombosis or cardiac surgery, the extent of MPTP opening determines the amount of irreversible damage (infarct size). Furthermore, cardioprotection can be achieved by inhibiting MPTP opening either directly with cyclosporin A analogues, or indirectly by reducing oxidative stress. The detailed molecular mechanism of the MPTP remains uncertain. Knockout studies have confirmed important regulatory roles for cyclophilin-D (CyP-D) and the adenine nucleotide translocase (ANT) but not the voltage dependent anion channel. Our own studies have implicated a calcium-triggered conformational change of the mitochondrial phosphate carrier that is facilitated by CyP-D and modulated by the conformation of the ANT.

    更新日期:2019-11-01
  • Functional characterization of a Drosophila mitochondrial uncoupling protein.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2004-09-01
    Yih-Woei C Fridell,Adolfo Sánchez-Blanco,Brian A Silvia,Stephen L Helfand

    Sequence alignment of conserved signature motifs predicts the existence of the uncoupling protein 5 (UCP5)/brain mitochondrial carrier protein (BMCP1) homologue in Drosophila melanogaster. Here we demonstrate the functional characterization of the Drosophila melanogaster UCP5 protein (DmUCP5) in the heterologous yeast system, the first insect UCP reported to date. We show that physiological levels of DmUCP5 expression are responsible for an increase in state 4 respiration rates and a decrease in mitochondrial membrane potential. Furthermore, similar to UCP1, UCP2, and UCP3, the uncoupling activity of DmUCP5 is augmented by fatty acids and inhibited by the purine nucleotide GDP. Thus, DmUCP5 shares the mechanisms known to regulate the UCPs characterized to date. A lack of growth inhibition observed in DmUCP5 expressing yeast is consistent with the notion that physiological uncoupling has a minimal effect on cell growth. Finally, semiquantitative RT-PCR analysis shows a distinctive pattern of DmUCP5 expression predominantly localized in the adult head, similar to the expression pattern of its mammalian homologues. The conserved regulation of the expression of this gene from mammals to fruit flies suggests a role for UCP5 in the brain.

    更新日期:2019-11-01
  • The road to the crystal structure of the cytochrome bc1 complex from the anoxigenic, photosynthetic bacterium Rhodobacter sphaeroides.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2008-10-28
    Di Xia,Lothar Esser,Maria Elberry,Fei Zhou,Linda Yu,Chang-An Yu

    The advantages of using bacterial systems to study the mechanism and function of cytochrome bc (1) complexes do not extend readily to their structural investigations. High quality crystals of bacterial complexes have been difficult to obtain despite the enzymes' smaller sizes and simpler subunit compositions compared to their mitochondrial counterparts. In the course of the structure determination of the bc (1) complex from R. sphaeroides, we observed that the growth of only low quality crystals correlated with low activity and stability of the purified complex, which was mitigated in part by introducing a double mutations to the enzyme. The S287R(cyt b)/V135S(ISP) mutant shows 40% increase in electron transfer activity and displays a 4.3 degrees C increase in thermal stability over wild-type enzyme. The amino acid histidine was found important in maintaining structural integrity of the bacterial complex, while the respiratory inhibitors such as stigmatellin are required for immobilization of the iron-sulfur protein extrinsic domain. Crystal quality of the R. sphaeroides bc (1) complex can be improved further by the presence of strontium ions yielding crystals that diffracted X-rays to better than 2.3 A resolution. The improved crystal quality can be understood in terms of participation of strontium ions in molecular packing arrangement in crystal.

    更新日期:2019-11-01
  • VDAC regulation: role of cytosolic proteins and mitochondrial lipids.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 2008-07-26
    Tatiana K Rostovtseva,Sergey M Bezrukov

    It was recently asserted that the voltage-dependent anion channel (VDAC) serves as a global regulator, or governor, of mitochondrial function (Lemasters and Holmuhamedov, Biochim Biophys Acta 1762:181-190, 2006). Indeed, VDAC, positioned on the interface between mitochondria and the cytosol (Colombini, Mol Cell Biochem 256:107-115, 2004), is at the control point of mitochondria life and death. This large channel plays the role of a "switch" that defines in which direction mitochondria will go: to normal respiration or to suppression of mitochondria metabolism that leads to apoptosis and cell death. As the most abundant protein in the mitochondrial outer membrane (MOM), VDAC is known to be responsible for ATP/ADP exchange and for the fluxes of other metabolites across MOM. It controls them by switching between the open and "closed" states that are virtually impermeable to ATP and ADP. This control has dual importance: in maintaining normal mitochondria respiration and in triggering apoptosis when cytochrome c and other apoptogenic factors are released from the intermembrane space into the cytosol. Emerging evidence indicates that VDAC closure promotes apoptotic signals without direct involvement of VDAC in the permeability transition pore or hypothetical Bax-containing cytochrome c permeable pores. VDAC gating has been studied extensively for the last 30 years on reconstituted VDAC channels. In this review we focus exclusively on physiologically relevant regulators of VDAC gating such as endogenous cytosolic proteins and mitochondrial lipids. Closure of VDAC induced by such dissimilar cytosolic proteins as pro-apoptotic tBid and dimeric tubulin is compared to show that the involved mechanisms are rather distinct. While tBid mostly modulates VDAC voltage gating, tubulin blocks the channel with the efficiency of blockage controlled by voltage. We also discuss how characteristic mitochondrial lipids, phospatidylethanolamine and cardiolipin, could regulate VDAC gating. Overall, we demonstrate that VDAC gating is not just an observation made under artificial conditions of channel reconstitution but is a major mechanism of MOM permeability control.

    更新日期:2019-11-01
  • Probes for energy transduction in membranes.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1976-10-01
    A Azzi,C Montecucco

    更新日期:2019-11-01
  • Adenylate regulation of photosynthetic electron transport and the coupling sites of phosphorylation in spinach chloroplasts.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1976-10-01
    T Yagi,Y Mukohata

    The regulation by adenylates of activities of various partial electron transport systems in spinach chloroplasts was studied using systems from H2O to 2,5-dimethyl-p-benzoquinone, H2O to 2,6-dichlorophenolindophenol, reduced 2,6-dichlorophenolindophenol to methyl viologen, and H2O to methyl viologen or ferricyanide. Adenylates regulated all of them. The ratio of the amount of esterified Pi (P) to that of electrons transported (Deltae) in coupling with phosphorylation manifested that there are two phosphorylation sites: one between H2O and 2,5-dimethyl-p-benzoquinone or 2,6-dichlorophenolindophenol and another between reduced 2,6-dichlorophenolindophenol and methyl viologen, under the proposed stoichiometries, i.e., P/DeltaH+ = 0.5 and DeltaH+/Deltae = 1, where DeltaH+ is the amount of protons pumped by electron transport (= those translocated during phosphorylation), when the basal electron transport (the part not regulated by adenylates) was excluded. The effects of pH, phlorizin, and methylamine on the adenylate regulation of electron transport, and the stimulation profile of electron transport coupled with quasiarsenylation suggested no distinction between the two phosphorylation sites.

    更新日期:2019-11-01
  • Thyroid hormone action on mitochondria. IV. Redox states of intrinsic pyridine nucleotides in hypothyroidism, and influence of L-thyroxine.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1976-10-01
    F L Hoch

    Measurements of fluorescence at >420 nm and extracted NADPH in mitochondria obtained from the livers of hypothyroid rats show that the addition of Pi, ADP and glutamate rapidly reduces over 90% of the total reducible intrinsic pyridine nucleotides in State 3, compared with 20% in normals. The total fluorescence intensity change and reducible NADP+ is about twice normal in hypothyroid mitochondria. Adding 6-30 microM L-thyroxine to hypothyroid mitochondria in vitro decreases and delays the substrate-induced reduction of pyridine nucleotides, and excludes both NADP+ from such reduction and NADPH from oxidation by added ADP + Pi, without changing the high NADP(H) content. The correcting actions of the hormone are rapidly reversed by albumin, probably by binding free hormone. Changes in respiration do not appear to account for these observations. There is indirect evidence for decreased phosphorylation of added ADP in hypothyroid mitochondria, and a correction by added hormone. The hormonal actions on NADP(H) redox reactions are not reproduced by 1 to 6 microM dinitrophenol in vitro. L-Thyroxine appears to specifically block the participation of NADP(H) in redox reactions in mitochondria from hypothyroid rats, perhaps by effecting a sequestration of the nucleotide, by inhibiting the pyridine nucleotide transhydrogenase, or by activating an energy-linked process that competes with transhydrogenation.

    更新日期:2019-11-01
  • Enzymatic hydrolysis of ATP and e-ATP by F-actin.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1976-10-01
    H Asai,M Asai

    Enzymatic hydrolysis of e-ATP by F-actin with and without application of sonic vibration at various pHs was investigated and compared with that of ATP. There was no significant difference on enzymatic activity between F-actin-bound e-ADP and F-actin-bound ADP. The hydrolysis rate of e-ATP under sonic vibration decreases monotonically with decreasing pH, similar to that of ATP. The magnitude of e-ATP hydrolysis rate was, however, about one third of that of ATP hydrolysis rate in the pH range between 6.3 and 8.5. Enzymatic hydrolysis of e-ATP without sonic vibration at room or higher temperatures decreases monotonically with increasing pH and becomes almost negligible at pH 8.5. The pH profile and the magnitude of enzymatic hydrolysis without sonic vibration were similar with ATP. Since the fluorescence intensity of e-ATP at 410 nm is enhanced by the binding with G-actin, the exchange binding affinity of e-ATP to G-actin which can be measured fluorophotometrically was about one third of that of ATP.

    更新日期:2019-11-01
  • Lipid requirement of membrane-bound enzymes.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1977-12-01
    P Gazzotti,S W Peterson

    更新日期:2019-11-01
  • Modification of amino acid and sugar transport in uncoupler-adapted Euglena gracilis.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1977-12-01
    J S Kahn,R T McConnell

    Uncoupler-adapted Euglena gracilis have a greatly impaired capacity to take up and incorporate some exogenously supplied amino acids and sugars. The degree of inhibition varies widely from >90% in the case of valine or glucose to none in the case of histidine. The inhibition is due to a decreased activity of the transport mechanism itself and is not due to either a lesion in the control mechanism for endogenous amino acid or sugar synthesis nor to a direct inhibition of the transport mechanism by uncouplers. No preferential labeling of mitochondrial membranes by [14C]amino acids occurs during the process of adaptation, a time when no cell division occurs. Apparently, during the long time required for adaptation, there occurs no major modification of mitochondrial proteins which could explain the subsequent resistance to uncouplers.

    更新日期:2019-11-01
  • Binding and reaction studies with adenine nucleotides on purified coupling factor from Rhodospirillum rubrum.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1977-12-01
    M E Hofmann,R Bachofen

    Equilibrium binding studies with ATPase isolated from Rhodospirillum rubum chromotophores have been carried out using gel filtration. Binding experiments with variable concentrations of [14C]ADP show a biphasic saturation curve. With a parameter fitting computer program the dissociation constants for two distinct binding sites are determined as 7 x 10(-6) and 9 x 10(-5) M, respectively. The enzyme-bound radioactivity is recovered as ADP (80-90%), and the rest is converted to AMP and ATP. In the free nucleotides a large amount of AMP (about 70%) is found in addition to ADP. Analogous binding experiments with [14C]ATP are monophasic. Most of the bound radioactivity can be identified as ADP showing a dissociation constant corresponding to the high affinity site. The pattern of the free nucleotides is the same as in the experiments with ADP. These results indicate three separate binding sites on the enzyme: a low and a high affinity site for ADP, and a site at which ATP hydrolysis takes place. The analysis of the nucleotides suggests for the ADP sites a phosphoryl group transfer to produce ATP and AMP. Various experiments exclude the contamination of the enzyme preparation with adenylate kinase.

    更新日期:2019-11-01
  • Physiological correlates of calcium-accumulating properties of mitochondria: fish-muscle mitochondria.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1977-12-01
    H R Sulochana,I Bashyam,S Narayan,J Jayaraman

    The mitochondria isolated from the muscles of fish acclimated to grow in different salinities have been studied with reference to their Ca2+ uptake capacity and compared to those isolated from fresh-water fish muscle. The results show a drastic response by the mitochondria with reference to their Ca2+ uptake function soon after exposure to the stress. Evidence is also presented to suggest an alteration in conformation. This perturbation appears to be the initial response to the stress since the normal state (as that of the fresh-water fish) is restored in course of time. Further, so far there is no indication that the electron transport function and ATP production are affected by the ionic stress conditions. This would support the physiological relevance of the mitochondrial capacity for Ca2+ uptake.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Evidence for the presence and role of tightly bound adenine nucleotides in phospholipid-free purified Micrococcus lysodeikticus adenosine triphosphatase.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1977-10-01
    C Muñoz,P Palacios,E Muñoz

    [32P]-labeled ATPase was isolated in a highly purified state from Micrococcus lysodeikticus strain PNB grown in medium supplemented with [32P]orthophosphate. Selective extraction procedures allowed us to determine that at least 25% of the firmly bound label belonged to adenine nucleotides, ATP and ADP being present in equimolar amounts. However, no 32P label was found to be part of phospholipids. This was confirmed by purification of the ATPase from cells fed with [2-3H]glycerol. Using the luciferin-luciferase assay we estimated that ATPase freshly isolated by Sephadex chromatography (specific activity 10-14 micromole substrate transformed x min(-1) x mg protein(-1)) contained 2 moles ATP/mole of enzyme. The ratio fell with the age of enzyme and its purification by gel electrophoresis and this was paralleled by a loss of ATPase activity. The endogenous nucleotides were readily exchanged by added ADP or ATP. This result suggests that the sites for tight binding of adenine nucleotides are equivalent, although ADP seems to have a higher affinity for them. The last properties represent a peculiar characteristic of this bacterial ATPase as compared with other bacterial and organelle energy-transducing proteins.

    更新日期:2019-11-01
  • Electrical properties and structural transitions in the mitochondrion.
    J. Bioenerg. Biomembr. (IF 2.548) Pub Date : 1977-10-01
    D D Eley,N C Lockhart,C N Richardson

    Charge carrier generation and transport in the mitochondrial lipoprotein system has been investigated by electrical conductivity, low frequency dielectric relaxation, and thermoelectric power. A parallel study was conducted on morphological/structural changes by DTA and NMR. The results obtained confirm the need to consider concurrently free charge carrier processes and polarization phenomena. All techniques show a "transition" at the same temperature. The steady state conductivity is correlated with main chain segmental reorientations of the phospholipid moiety below the transition and with an interfacial polarization process above it. The Seebeck coefficient provides a useful new aid to characterizing the charge carriers, confirming that they are electronic. The terminal cytochrome oxidase component was investigated separately but it largely reflected ionic impurities characteristic of the isolation process, so that the results were of no intrinsic value.

    更新日期:2019-11-01
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