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  • Selective Autophagy: the Rise of the Zebrafish Model
    Autophagy (IF 9.77) Pub Date : 2020-11-24
    Devesh C. Pant; Taras Y. Nazarko

    Abstract Selective autophagy is a specific elimination of certain intracellular substrates by autophagic pathways. The most studied macroautophagy pathway involves tagging and recognition of a specific cargo by the autophagic membrane (phagophore) followed by the complete sequestration of targeted cargo from the cytosol by the double-membrane vesicle, autophagosome. Until recently, the knowledge about

  • GLIPR2 is a negative regulator of autophagy and the BECN1-ATG14-containing phosphatidylinositol 3-kinase complex
    Autophagy (IF 9.77) Pub Date : 2020-11-23
    Yuting Zhao; Zhongju Zou; Daxiao Sun; Yue Li; Sangita C. Sinha; Li Yu; Lynda Bennett; Beth Levine

    ABSTRACT A key mediator of macroautophagy/autophagy induction is the class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1) consisting of PIK3C3/VPS34, PIK3R4/VPS15, BECN1, and ATG14. Although several proteins are known to enhance or decrease PtdIns3K-C1 activity, our understanding of the molecular regulation of PtdIns3K-C1 is still incomplete. Previously, we identified a Golgi-associated

  • A tecpr2 knockout mouse exhibits age-dependent neuroaxonal dystrophyassociated with autophagosome accumulation
    Autophagy (IF 9.77) Pub Date : 2020-11-20
    Bat-Chen Tamim-Yecheskel; Milana Fraiberg; Kamilya Kokabi; Saskia Freud; Oren Shatz; Letizia Marvaldi; Nemanja Subic; Ori Brenner; Michael Tsoory; Raya Eilam-Altstadter; Inbal Biton; Alon Savidor; Nili Dezorella; Gali Heimer; Christian Behrends; Bruria Ben-Zeev; Zvulun Elazar

    Abstract Mutations in the coding sequence of human TECPR2 were recently linked to spastic paraplegia type 49 (SPG49), a hereditary neurodegenerative disorder involving intellectual disability, autonomic-sensory neuropathy, chronic respiratory disease and decreased pain sensitivity. Here, we report the generation of a novel CRISPR-Cas9 tecpr2 knockout (tecpr2 −/−) mouse that exhibits behavioral pathologies

  • Alternative mitochondrial quality control mediated by extracellular release
    Autophagy (IF 9.77) Pub Date : 2020-11-20
    Chi-Jing Choong; Tatsusada Okuno; Kensuke Ikenaka; Kousuke Baba; Hideki Hayakawa; Masato Koike; Mutsumi Yokota; Junko Doi; Keita Kakuda; Toshihide Takeuchi; Akiko Kuma; Shuhei Nakamura; Yoshitaka Nagai; Seiichi Nagano; Tamotsu Yoshimori; Hideki Mochizuki

    Abstract Mitochondrial quality control, which is crucial for maintaining cellular homeostasis, has been considered to be achieved exclusively through mitophagy. Here we report an alternative mitochondrial quality control pathway mediated by extracellular mitochondria release. By performing time-lapse confocal imaging on a stable cell line with fluorescent-labeled mitochondria, we observed release of

  • Lysosomal targeting of autophagosomes by the TECPR domain of TECPR2
    Autophagy (IF 9.77) Pub Date : 2020-11-19
    Milana Fraiberg; Bat-Chen Tamim-Yecheskel; Kamilya Kokabi; Nemanja Subic; Gali Heimer; Franziska Eck; Karsten Nalbach; Christian Behrends; Bruria Ben-Zeev; Oren Shatz; Zvulun Elazar

    Abstract TECPR2 (tectonin beta-propeller repeat containing 2) is a large, multi-domain protein comprised of an amino-terminal WD domain, a middle unstructured region and a carboxy-terminal TEPCR domain comprises of six TECPR repeats followed by a functional LIR motif. Human TECPR2 mutations are linked to spastic paraplegia type 49 (SPG49), a hereditary neurodegenerative disorder. Here we show that

  • Pancreas-specific SNAP23 Depletion Prevents Pancreatitis by Attenuating Pathological Basolateral Exocytosis and Formation of Trypsin-activating Autolysosomes.
    Autophagy (IF 9.77) Pub Date : 2020-11-19
    Subhankar Dolai; Toshimasa Takahashi; Tairan Qin; Tao Liang; Li Xie; Fei Kang; Yi-Fan Miao; Huanli Xie; Youhou Kang; Justin Manuel; Erin Winter; Paul A. Roche; Mark S. Cattral; Herbert Y. Gaisano

    ABSTRACT Intrapancreatic trypsin activation by dysregulated macroautophagy/autophagy and pathological exocytosis of zymogen granules (ZGs), along with activation of inhibitor of NFKB/NF-κB kinase (IKK) are necessary early cellular events in pancreatitis. How these three pancreatitis events are linked is unclear. We investigated how SNAP23 orchestrates these events leading to pancreatic acinar injury

  • MAPK1/3 kinase-dependent ULK1 degradation attenuates mitophagy and promotes breast cancer bone metastasis
    Autophagy (IF 9.77) Pub Date : 2020-11-19
    Rong Deng; Hai-Liang Zhang; Jun-Hao Huang; Rui-Zhao Cai; Yan Wang; Yu-Hong Chen; Bing-Xin Hu; Zhi-Peng Ye; Zhi-Ling Li; Jia Mai; Yun Huang; Xuan Li; Xiao-Dan Peng; Gong-Kan Feng; Jun-Dong Li; Jun Tang; Xiao-Feng Zhu

    Abstract The function of mitophagy in cancer is controversial. ULK1 is critical for induction of macroautophagy/autophagy and has a more specific role in mitophagy in response to hypoxia. Here, we show that ULK1 deficiency induces an invasive phenotype of breast cancer cells under hypoxia and increases osteolytic bone metastasis. Mechanistically, ULK1 depletion attenuates mitophagy ability during hypoxia

  • Enhanced viability and function of mesenchymal stromal cell spheroids is mediated via autophagy induction
    Autophagy (IF 9.77) Pub Date : 2020-11-18
    Shobha Regmi; Pawan Kumar Raut; Shiva Pathak; Prakash Shrestha; Pil-Hoon Park; Jee-Heon Jeong

    ABSTRACT Mesenchymal stromal cells (MSCs) have received attention as promising therapeutic agents for the treatment of various diseases. However, poor post-transplantation viability has been a major hurdle in MSC-based therapy, despite encouraging results in many inflammatory disorders and tissue repair. Recently, three dimensional (3D)-cultured MSCs (MSC3D) were shown to have higher cell survival

  • TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation
    Autophagy (IF 9.77) Pub Date : 2020-11-16
    Hee-Seon Park; Ji-Won Song; Jin-Ho Park; Byung-Kwan Lim; Og-Sung Moon; Hwa-Young Son; Jae-Hyuk Lee; Bin Gao; Young-Suk Won; Hyo-Jung Kwon

    ABSTRACT Impaired macroautophagy/autophagy has been implicated in experimental and human nonalcoholic steatohepatitis (NASH). However, the mechanism underlying autophagy dysregulation in NASH is largely unknown. Here, we investigated the role and mechanism of TXNIP/VDUP1 (thioredoxin interacting protein), a key mediator of cellular stress responses, in the pathogenesis of NASH. Hepatic TXNIP expression

  • Post translational modifications in Tuberculosis: Ubiquitination Paradox
    Autophagy (IF 9.77) Pub Date : 2020-11-15
    Mohd Shariq; Neha Quadir; Javaid Ahmad Sheikh; Alok Kumar Singh; William R. Bishai; Nasreen Z. Ehtesham; Seyed E. Hasnain

    Abstract Innate immune signaling and xenophagy are crucial innate defense strategies exploited by the host to counteract intracellular pathogens with ubiquitination as a critical regulator of these processes. These pathogens, including Mycobacterium tuberculosis (M. tb), co-opt the host ubiquitin machinery by utilizing secreted or cell surface effectors to dampen innate host defenses. Inversely, the

  • Protein complexes and neighborhoods driving autophagy
    Autophagy (IF 9.77) Pub Date : 2020-11-13
    Devanarayanan Siva Sankar; Jörn Dengjel

    ABSTRACT Autophagy summarizes evolutionarily conserved, intracellular degradation processes targeting cytoplasmic material for lysosomal degradation. These encompass constitutive processes as well as stress responses, which are often found dysregulated in diseases. Autophagy pathways help in the clearance of damaged organelles, protein aggregates and macromolecules, mediating their recycling and maintaining

  • A VASt-domain protein regulates autophagy, membrane tension, and sterol homeostasis in rice blast fungus
    Autophagy (IF 9.77) Pub Date : 2020-11-11
    Xue-Ming Zhu; Lin Li; Ying-Ying Cai; Xi-Yu Wu; Huan-Bin Shi; Shuang Liang; Ying-Min Qu; Naweed I. Naqvi; Maurizio Del Poeta; Bo Dong; Fu-Cheng Lin; Xiao-Hong Liu

    Abstract Sterols are a class of lipids critical for fundamental biological processes and membrane dynamics. These molecules are synthesized in the endoplasmic reticulum (ER) and are transported bi-directionally between the ER and plasma membrane (PM). However, the trafficking mechanism of sterols and their relationship with macroautophagy/autophagy are still poorly understood in the rice blast fungus

  • AMPK-induced autophagy as a key regulator of cell migration
    Autophagy (IF 9.77) Pub Date : 2020-11-10
    Bressan Cedric; Saghatelyan Armen

    Abstract Cell migration is a highly dynamic and energy-intensive process that ensures the correct targeting of cells during embryonic and postnatal development. In recent work, we highlighted the importance of macroautophagy/autophagy in regulating the dynamics of cell migration under baseline conditions and in response to a diverse set of molecular factors. Genetic suppression of autophagy-related

  • Hydrogen peroxide mediates spermidine-induced autophagy to alleviate salt stress in cucumber
    Autophagy (IF 9.77) Pub Date : 2020-11-10
    Yuemei Zhang; Yu Wang; Wenxu Wen; Zhengrong Shi; Qinsheng Gu; Golam Jalal Ahammed; Kai Cao; Mohammad Shah Jahan; Sheng Shu; Jian Wang; Jin Sun; Shirong Guo

    Abstract Autophagy, an evolutionally conserved cellular degradation process, plays critical roles in plant development and stress response. Despite the wealth of information on the vital role of autophagy in responses to environmental stresses, little is known about the regulation of autophagy. In this study, we demonstrated that spermidine (Spd), a kind of polyamine, was involved in the regulation

  • ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota
    Autophagy (IF 9.77) Pub Date : 2020-11-10
    Sup Kim; June-Young Lee; Seul Gi Shin; Jin Kyung Kim; Prashanta Silwal; Young Jae Kim; Na-Ri Shin; Pil Soo Kim; Minho Won; Sang-Hee Lee; Soo Yeon Kim; Miwa Sasai; Masahiro Yamamoto; Jin-Man Kim; Jin-Woo Bae; Eun-Kyeong Jo

    ABSTRACT The orphan nuclear receptor ESRRA (estrogen related receptor alpha) is critical in mitochondrial biogenesis and macroautophagy/autophagy function; however, the roles of ESRRA in intestinal function remain uncharacterized. Herein we identified that ESRRA acts as a key regulator of intestinal homeostasis by amelioration of colonic inflammation through activation of autophagic flux and control

  • HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1
    Autophagy (IF 9.77) Pub Date : 2020-11-10
    Manuela Antonioli; Benedetta Pagni; Tiziana Vescovo; Rob Ellis; Benjamin Cosway; Francesca Rollo; Veronica Bordoni; Chiara Agrati; Marie Labus; Renato Covello; Maria Benevolo; Giuseppe Ippolito; Max Robinson; Mauro Piacentini; Penny Lovat; Gian Maria Fimia

    Abstract Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favourable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPV-positive OPSCC cells display reduced macroautophagy/autophagy activity, mediated

  • Equine lentivirus counteracts SAMHD1 restriction by Rev-mediated degradation of SAMHD1 via the BECN1-dependent lysosomal pathway
    Autophagy (IF 9.77) Pub Date : 2020-11-10
    Huiling Ren; Xin Yin; Chao Su; Miaomiao Guo; Xue-Feng Wang; Lei Na; Yuezhi Lin; Xiaojun Wang

    Abstract The innate immune restriction factor SAMHD1 can inhibit diverse viruses in myeloid cells. Mechanistically, SAMHD1 inhibits lentiviral replication including HIV-1 by depleting the nucleotide pool to interfere with their reverse transcription. Equine infectious anemia virus (EIAV) is an ancient lentivirus that preferentially attacks macrophages. However, the mechanism by which EIAV successfully

  • Macrophage mitochondrial MFN2 (mitofusin 2) links immune stress and immune response through reactive oxygen species (ROS) production
    Autophagy (IF 9.77) Pub Date : 2020-11-10
    Jorge Lloberas; Juan P. Muñoz; María Isabel Hernández-Álvarez; Pere-Joan Cardona; Antonio Zorzano; Antonio Celada

    ABSTRACT MFN2 (mitofusin 2) is required for mitochondrial fusion and for mitochondria-endoplasmic reticulum interaction. Using myeloid-conditional KO mice models, we found that MFN2 but not MFN1 is a prerequisite for the adaptation of mitochondrial respiration to stress conditions as well as for the production of reactive oxygen species (ROS). The deficient ROS production in the absence of MFN2 impairs

  • Regulation and Function of Autophagy in Pancreatic Cancer
    Autophagy (IF 9.77) Pub Date : 2020-11-08
    Jingbo Li; Xin Chen; Rui Kang; Herbert Zeh; Daniel J. Klionsky; Daolin Tang

    Abstract Oncogenic KRAS mutation-driven pancreatic ductal adenocarcinoma is currently the fourth-leading cause of cancer-related deaths in the United States. Macroautophagy (hereafter “autophagy”) is one of the lysosome-dependent degradation systems that can remove abnormal proteins, damaged organelles, or invading pathogens by activating dynamic membrane structures (e.g., phagophores, autophagosomes

  • Measurement of autophagic flux in humans: an optimized method for blood samples
    Autophagy (IF 9.77) Pub Date : 2020-11-08
    Julien Bensalem; Kathryn J Hattersley; Leanne K Hein; Xiao Tong Teong; Julian M Carosi; Sofia Hassiotis; Randall H Grose; Célia Fourrier; Leonie K Heilbronn; Timothy J Sargeant

    Abstract Autophagic flux is a critical cellular process that is vastly under-appreciated in terms of its importance to human health. Preclinical studies have demonstrated that reductions in autophagic flux cause cancer and exacerbate chronic diseases, including heart disease and the pathological hallmarks of dementia. Autophagic flux can be increased by targeting nutrition-related biochemical signaling

  • C53 is a cross-kingdom conserved reticulophagy receptor that bridges the gap betweenselective autophagy and ribosome stalling at the endoplasmic reticulum
    Autophagy (IF 9.77) Pub Date : 2020-11-08
    Madlen Stephani; Lorenzo Picchianti; Yasin Dagdas

    Abstract Reticulophagy, the autophagic degradation of the endoplasmic reticulum, is crucial to maintain ER homeostasis during stress. Although several reticulophagy receptors have been discovered recently, most of them have been studied using nutrient starvation. How macroautophagy/autophagy cross-talks with other ER-quality control mechanisms is largely unknown. Using ATG8-based affinity proteomics

  • Atg11-mediated activation of Atg1 kinase in fission yeast
    Autophagy (IF 9.77) Pub Date : 2020-11-08
    Zhao-Qian Pan; Li-Lin Du

    Abstract The protein kinase Atg1 is a key player in macroautophagy/autophagy, but how its activity is regulated in various organisms is inadequately understood. Our recent study showed that in the fission yeast Schizosaccharomyces pombe, Atg1 kinase activity depends on Atg11, but not Atg13, Atg17, or Atg101. Notably, a 62 amino acid region of S. pombe Atg11 is sufficient for activating Atg1. This region

  • Highlights in the fight against COVID-19: does autophagy play a role in SARS-CoV-2 infection?
    Autophagy (IF 9.77) Pub Date : 2020-11-05
    Elizabeth Delorme-Axford; Daniel J. Klionsky

    ABSTRACT In the preceding months, the novel SARS-CoV-2 pandemic has devastated global communities. The need for safe and effective prophylactic and therapeutic treatments to combat COVID-19 – the human disease resulting from SARS-CoV-2 infection – is clear. Here, we present recent developments in the effort to combat COVID-19 and consider whether SARS-CoV-2 may potentially interact with the host autophagy

  • Autophagy-independent function of lipidated LC3 essential for TFEB activation during the lysosomal damage responses
    Autophagy (IF 9.77) Pub Date : 2020-11-05
    Shuhei Nakamura; Shiori Akayama; Tamotsu Yoshimori

    Abstract Lysosomes are digestive organelles in cells containing many hydrolases, and also serve as a signaling hub to integrate intracellular and extracellular inputs; therefore, the integrity of lysosomes is critical for cellular homeostasis. Many agents and conditions can damage lysosomal membranes, which lead to leakage of lysosomal acidic contents into the cytosol thus becoming harmful for cells

  • Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3
    Autophagy (IF 9.77) Pub Date : 2020-11-04
    Zheng-Zhao Liu; Chun-Gu Hong; Wen-Bao Hu; Meng-Lu Chen; Ran Duan; Hong-Ming Li; Tao Yue; Jia Cao; Zhen-Xing Wang; Chun-Yuan Chen; Xiong-Ke Hu; Ben Wu; Hao-Ming Liu; Yi-Juan Tan; Jiang-Hua Liu; Zhong-Wei Luo; Yan Zhang; Shan-Shan Rao; Ming-Jie Luo; Hao Yin; Yi-Yi Wang; Kun Xia; Lang Xu; Si-Yuan Tang; Rong-Gui Hu; Hui Xie

    ABSTRACT Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate

  • Structure of human ATG9A: how holey art thou?
    Autophagy (IF 9.77) Pub Date : 2020-08-25
    Wayne D Hawkins,Daniel J Klionsky

    ABSTRACT Several studies have provided insight into the unique intracellular localization, dynamic trafficking and diverse repertoire of binding partners of Atg9/ATG9, but structural details of the protein have remained elusive. Guardia and colleagues now report the structure of human ATG9A to a resolution of 2.9 Å, revealing, among other features, an elaborate system of tunnels permeating the ATG9A

  • Two different axes CALCOCO2-RB1CC1 and OPTN-ATG9A initiate PRKN-mediated mitophagy.
    Autophagy (IF 9.77) Pub Date : 2020-09-07
    Koji Yamano,Richard J Youle

    ABSTRACT PINK1 and PRKN, proteins mutated in Parkinson disease, selectively amplify ubiquitin signals on damaged mitochondria for elimination via mitophagy. Because all five macroautophagy/autophagy receptors in mammals possess domains binding to ubiquitin and Atg8-family proteins, they were thought to recruit Atg8-family protein labeled phagophores from a cytosolic pool. However, our recent findings

  • Lighting up the fire in cold tumors to improve cancer immunotherapy by blocking the activity of the autophagy-related protein PIK3C3/VPS34.
    Autophagy (IF 9.77) Pub Date : 2020-09-05
    Bassam Janji,Meriem Hasmim,Santiago Parpal,Angelo De Milito,Guy Berchem,Muhammad Zaeem Noman

    ABSTRACT Cancer immunotherapy based on Immune checkpoint blockade (ICB) is a promising strategy to treat patients with advanced highly aggressive therapy-resistant tumors. Unfortunately, the clinical reality is that only a small number of patients benefit from the remarkable clinical remissions achieved by ICB. Experimental and clinical evidence claimed that durable clinical benefit observed using

  • Epr1, a UPR-upregulated soluble autophagy receptor for reticulophagy.
    Autophagy (IF 9.77) Pub Date : 2020-09-05
    Dan Zhao,Li-Lin Du

    ABSTRACT The endoplasmic reticulum (ER) is a major site of protein folding. Perturbations in the folding capacity of the ER result in ER stress. ER stress triggers autophagic degradation of the ER (reticulophagy). Molecular mechanisms underlying ER stress-induced reticulophagy remain largely unknown. Our recent study identified a soluble protein, Epr1, as an autophagy receptor for ER stress-induced

  • Proteasome malfunction activates the PPP3/calcineurin-TFEB-SQSTM1/p62 pathway to induce macroautophagy in the heart.
    Autophagy (IF 9.77) Pub Date : 2020-09-22
    Huabo Su,Xuejun Wang

    ABSTRACT Proteasome inhibition (PSMI) is known to activate macroautophagy (autophagy hereafter), but the underlying mechanisms remain to be fully delineated. Here we discuss our recent work identifying an important PPP3/calcineurin-TFEB-SQSTM1/p62 pathway in mediating activation of autophagy by PSMI, a compensatory process for the heart with proteasome malfunction. Through increasing PPP3/calcineurin

  • Corrigendum for circHIPK2.
    Autophagy (IF 9.77) Pub Date : 2020-09-16

    (2020). Corrigendum for circHIPK2. Autophagy: Vol. 16, No. 11, pp. 2117-2118.

  • Corrigendum: Engagement of Circular RNA HECW2 in the Nonautophagic Role of ATG5 Implicated in the Endothelial-Mesenchymal Transition.
    Autophagy (IF 9.77) Pub Date : 2020-09-18

    (2020). Corrigendum: Engagement of Circular RNA HECW2 in the Nonautophagic Role of ATG5 Implicated in the Endothelial-Mesenchymal Transition. Autophagy: Vol. 16, No. 11, pp. 2119-2119.

  • Corrigendum for miR-143/BBC.
    Autophagy (IF 9.77) Pub Date : 2020-09-16

    (2020). Corrigendum for miR-143/BBC. Autophagy: Vol. 16, No. 11, pp. 2120-2121.

  • Antidepressant drug sertraline modulates AMPK-MTOR signaling-mediated autophagy via targeting mitochondrial VDAC1 protein
    Autophagy (IF 9.77) Pub Date : 2020-10-30
    Hui-Yun Hwang; Joong Sup Shim; Dasol Kim; Ho Jeong Kwon

    Abstract Macroautophagy/autophagy (hereafter autophagy), the process of mass degradation of unnecessary elements within the cell, is often dysregulated in many diseases such as cancer, atherosclerosis, and neurodegenerative diseases. Hence, autophagy modulating agents have a great potential to be therapeutic agents for the autophagy-related diseases. Here we report that an anti-depressant drug sertraline

  • BECN2 (beclin 2)-mediated non-canonical autophagy in innate immune signaling and tumor development
    Autophagy (IF 9.77) Pub Date : 2020-10-29
    Motao Zhu; Guangtong Deng; Changsheng Xing; Guangjun Nie; Rong-Fu Wang

    ABSTRACT BECN2 (beclin 2) is a newly identified mammalian-specific macroautophagy/autophagy family member, and plays a critical role in the control of obesity and insulin sensitivity. However, its role in innate immune signaling and inflammation remains elusive. In our recent study, we show that BECN2 functions as a negative regulator in innate immune signaling and tumor development through non-canonical

  • A novel reticulophagy receptor, Epr1: a bridge between the phagophore protein Atg8 and ER transmembrane VAP proteins
    Autophagy (IF 9.77) Pub Date : 2020-10-29
    Ying Yang; Daniel J. Klionsky

    ABSTRACT Reticulophagy, a type of selective autophagy that specifically targets and degrades parts of the endoplasmic reticulum (ER) network (sheets or tubules), plays a crucial role in the responses to ER stress. The selectivity of the ER cargo recognition relies on the unique reticulophagy receptors, which tether and deliver cargos to phagophores, the precursors to autophagosomes. Various integral

  • PTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation
    Autophagy (IF 9.77) Pub Date : 2020-10-28
    He-Yen Chou; Yi-Tang Lee; Yuchieh Jay Lin; Jung-Kun Wen; Wen-Hsin Peng; Pei-Lien Hsieh; Shu-Yu Lin; Chin-Chun Hung; Guang-Chao Chen

    ABSTRACT Macroautophagy/autophagy is an evolutionarily conserved intracellular pathway for the degradation of cytoplasmic materials. Under stress conditions, autophagy is upregulated and double-membrane autophagosomes are formed by the expansion of phagophores. The ATG16L1 precursor fusion contributes to development of phagophore structures and is critical for the biogenesis of autophagosomes. Here

  • Cp1/cathepsin L is required for autolysosomal clearance in Drosophila
    Autophagy (IF 9.77) Pub Date : 2020-10-28
    Tianqi Xu; Shannon Nicolson; Jarrod J. Sandow; Sonia Dayan; Xin Jiang; Jantina A. Manning; Andrew I. Webb; Sharad Kumar; Donna Denton

    ABSTRACT Macroautophagy/autophagy is a highly conserved lysosomal degradative pathway important for maintaining cellular homeostasis. Much of our current knowledge of autophagy is focused on the initiation steps in this process. Recently, an understanding of later steps, particularly lysosomal fusion leading to autolysosome formation and the subsequent role of lysosomal enzymes in degradation and recycling

  • Sensitive ELISA-based detection method for the mitophagy marker p-S65-Ub in human cells, autopsy brain, and blood samples
    Autophagy (IF 9.77) Pub Date : 2020-10-28
    Jens O. Watzlawik; Xu Hou; Dominika Truban; Chloe Ramnarine; Sandeep K. Barodia; Tania F. Gendron; Michael G. Heckman; Michael DeTure; Joanna Siuda; Zbigniew K. Wszolek; Clemens R. Scherzer; Owen A. Ross; Guojun Bu; Dennis W. Dickson; Matthew S. Goldberg; Fabienne C. Fiesel; Wolfdieter Springer

    ABSTRACT Mitochondrial dysfunction is an early, imminent event in neurodegenerative disorders including Parkinson disease (PD) and Alzheimer disease (AD). The enzymatic pair PINK1 and PRKN/Parkin recognize and transiently label damaged mitochondria with ubiquitin (Ub) phosphorylated at Ser65 (p-S65-Ub) as a signal for degradation via the autophagy-lysosome system (mitophagy). Despite its discovery

  • ATF4 links ER stress with reticulophagy in glioblastoma cells
    Autophagy (IF 9.77) Pub Date : 2020-10-28
    Svenja Zielke; Simon Kardo; Laura Zein; Muriel Mari; Adriana Covarrubias-Pinto; Maximilian N. Kinzler; Nina Meyer; Alexandra Stolz; Simone Fulda; Fulvio Reggiori; Donat Kögel; Sjoerd J. L. van Wijk

    ABSTRACT Selective degradation of the endoplasmic reticulum (ER; reticulophagy) is a type of autophagy involved in the removal of ER fragments. So far, amino acid starvation as well as ER stress have been described as inducers of reticulophagy, which in turn restores cellular energy levels and ER homeostasis. Here, we explored the autophagy-inducing mechanisms that underlie the autophagic cell death

  • Extracellular SQSTM1 as an inflammatory mediator
    Autophagy (IF 9.77) Pub Date : 2020-10-28
    Borong Zou; Jiao Liu; Daniel J. Klionsky; Daolin Tang; Rui Kang

    ABSTRACT Excessive inflammation may lead to irreparable injury and even death, but the key mediators and underlying mechanisms remain unclear. Our recent findings indicate that SQSTM1/p62 (sequestosome 1), a well-known macroautophagy/autophagy receptor, is a lethal inflammatory mediator of sepsis and septic shock. The release of SQSTM1 occurs during tissue damage or microbial invasion through two main

  • Ischemia-induced Upregulation of Autophagy Preludes Dysfunctional Lysosomal Storage and Associated Synaptic Impairments in Neurons
    Autophagy (IF 9.77) Pub Date : 2020-10-28
    Xia Zhang; Mengping Wei; Jiahui Fan; Weijie Yan; Xu Zha; Huimeng Song; Rongqi Wan; Yanling Yin; Wei Wang

    Abstract Macroautophagy/autophagy is vital for neuronal homeostasis and functions. Accumulating evidence suggest that autophagy is impaired during cerebral ischemia, contributing to neuronal dysfunction and neurodegeneration. However, the outcomes after transient modification in autophagy machinery are not fully understood. This study investigated the effects of ischemic stress on autophagy and synaptic

  • Autophagy under construction: insights from in vitro reconstitution of autophagosome nucleation
    Autophagy (IF 9.77) Pub Date : 2020-10-23
    Shree Padma Metur; Daniel J. Klionsky

    ABSTRACT Macroautophagy/autophagy is a complex process that involves over 40 proteins in Saccharomyces cerevisiae. How these proteins are organized, and their activities orchestrated to facilitate an efficient autophagic mechanism remain elusive. Sawa-Makarsha et al. reconstitute the initial steps of autophagosome biogenesis during selective autophagy using autophagy factors purified from yeast. Their

  • Mir214-3p and Hnf4a/Hnf4α reciprocally regulate Ulk1 expression and autophagy in nonalcoholic hepatic steatosis
    Autophagy (IF 9.77) Pub Date : 2020-10-20
    Da-Hye Lee; So-Hyun Park; Jiyun Ahn; Seung Pyo Hong; Eunyoung Lee; Young-Jin Jang; Tae-Youl Ha; Yang Hoon Huh; Seung-Yeon Ha; Tae-Il Jeon; Chang Hwa Jung

    ABSTRACT Macroautophagy/autophagy, a self-degradative process, regulates metabolic homeostasis in response to various stress conditions and is a therapeutic target for nonalcoholic fatty liver disease. We found that autophagic activity was inhibited as a result of a significant reduction in the expression of autophagy-related genes such as Ulk1 in a mouse model and patients with fatty liver. This downregulation

  • HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death
    Autophagy (IF 9.77) Pub Date : 2020-10-19
    Coralie F Daussy; Mathilde Galais; Baptiste Pradel; Véronique Robert-Hebmann; Sophie Sagnier; Sophie Pattingre; Martine Biard-Piechaczyk; Lucile Espert

    ABSTRACT The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4+ T lymphocyte cell death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers macroautophagy/autophagy, a process necessary for subsequent apoptosis, and the production of reactive oxygen species (ROS) in bystander

  • Mammalian Atg8-family proteins are upstream regulators of the lysosomalsystem by controlling MTOR and TFEB
    Autophagy (IF 9.77) Pub Date : 2020-10-19
    Suresh Kumar; Ashish Jain; Seong Won Choi; Gustavo Peixoto Duarte da Silva; Lee Allers; Michal H. Mudd; Ryan Scott Peters; Jan Haug Anonsen; Tor-Erik Rusten; Michael Lazarou; Vojo Deretic

    Abstract Macroautophagy/autophagy delivers cytoplasmic cargo to lysosomes for degradation. In yeast, the single Atg8 protein plays a role in the formation of autophagosomes whereas in mammalian cells there are five to seven paralogs, referred to as mammalian Atg8s (mAtg8s: GABARAP, GABARAPL1, GABARAPL2, LC3A, LC3B, LC3B2 and LC3C) with incompletely defined functions. Here we show that a subset of mAtg8s

  • Autophagy unleashes noncanonical microRNA functions
    Autophagy (IF 9.77) Pub Date : 2020-10-15
    Donato Santovito; Virginia Egea; Kiril Bidzhekov; Lucia Natarelli; André Mourão; Xavier Blanchet; Kanin Wichapong; Maria Aslani; Coy Brunßen; Michael Horckmans; Michael Hristov; Arie Geerlof; Esther Lutgens; Mat J. A. P. Daemen; Tilman Hackeng; Christian Ries; Triantafyllos Chavakis; Henning Morawietz; Ronald Naumann; Philipp Von Hundelshausen; Sabine Steffens; Johan Duchêne; Remco T. A. Megens; Michael

    ABSTRACT MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which act by guiding AGO (argonaute) proteins to target RNA transcripts in the RNA-induced silencing complex (RISC). This macromolecular complex includes multiple additional components (e.g., TNRC6A) that allow for interaction with enzymes mediating inhibition of translation or RNA decay. However, miRNAs also reside

  • BNIP3L/Nix-induced mitochondrial fission, mitophagy, and impaired myocyte glucose uptake are abrogated by PRKA/PKA phosphorylation
    Autophagy (IF 9.77) Pub Date : 2020-10-12
    Simone C. da Silva Rosa; Matthew D. Martens; Jared T. Field; Lucas Nguyen; Stephanie M. Kereliuk; Yan Hai; Donald Chapman; William Diehl-Jones; Michel Aliani; Adrian R. West; James Thliveris; Saeid Ghavami; Christof Rampitsch; Vernon W. Dolinsky; Joseph W. Gordon

    ABSTRACT Lipotoxicity is a form of cellular stress caused by the accumulation of lipids resulting in mitochondrial dysfunction and insulin resistance in muscle. Previously, we demonstrated that the mitophagy receptor BNIP3L/Nix is responsive to lipotoxicity and accumulates in response to a high-fat (HF) feeding. To provide a better understanding of this observation, we undertook gene expression array

  • SSH1 impedes SQSTM1/p62 flux and MAPT/Tau clearance independent of CFL (cofilin) activation
    Autophagy (IF 9.77) Pub Date : 2020-10-12
    Cenxiao Fang; Jung-A A. Woo; Tian Liu; Xingyu Zhao; Sara Cazzaro; Yan Yan; Jenet Matlack; Teresa Kee; Patrick LePochat; David E. Kang

    ABSTRACT Accumulation of toxic protein assemblies and damaged mitochondria are key features of neurodegenerative diseases, which arise in large part from clearance defects in the Macroautophagy/autophagy-lysosome system. The autophagy cargo receptor SQSTM1/p62 plays a major role in the clearance of ubiquitinated cargo through Ser403 phosphorylation by multiple kinases. However, no phosphatase is known

  • SMAD3 promotes autophagy dysregulation by triggering lysosome depletion in tubular epithelial cells in diabetic nephropathy
    Autophagy (IF 9.77) Pub Date : 2020-10-12
    Chen Yang; Xiao-Cui Chen; Zhi-Hang Li; Hong-Luan Wu; Kai-Peng Jing; Xiao-Ru Huang; Lin Ye; Biao Wei; Hui-Yao Lan; Hua-Feng Liu

    ABSTRACT Macroautophagy/autophagy dysregulation has been noted in diabetic nephropathy; however, the regulatory mechanisms controlling this process remain unclear. In this study, we showed that SMAD3 (SMAD family member 3), the key effector of TGFB (transforming growth factor beta)-SMAD signaling, induces lysosome depletion via the inhibition of TFEB-dependent lysosome biogenesis. The pharmacological

  • Caty Casas (1967-2020)
    Autophagy (IF 9.77) Pub Date : 2020-10-12
    Patricia Boya

    (2020). Caty Casas (1967-2020). Autophagy. Ahead of Print.

  • Atg8-mediated super-assembly of Atg40 induces local ER remodeling in reticulophagy
    Autophagy (IF 9.77) Pub Date : 2020-10-10
    Keisuke Mochida; Hitoshi Nakatogawa

    ABSTRACT Reticulophagy (or ER-phagy) is a type of selective autophagy that targets the endoplasmic reticulum (ER). In the process of reticulophagy, part of the ER is fragmented and packed within autophagosomes. However, the underlying mechanism that induces this local remodeling of ER subdomains was poorly understood. Our recent study showed that in the budding yeast Saccharomyces cerevisiae the reticulophagy

  • Raft-like lipid microdomains drive autophagy initiation via AMBRA1-ERLIN1 molecular association within MAMs
    Autophagy (IF 9.77) Pub Date : 2020-10-09
    Valeria Manganelli; Paola Matarrese; Manuela Antonioli; Lucrezia Gambardella; Tiziana Vescovo; Christine Gretzmeier; Agostina Longo; Antonella Capozzi; Serena Recalchi; Gloria Riitano; Roberta Misasi; Joern Dengjel; Walter Malorni; Gian Maria Fimia; Maurizio Sorice; Tina Garofalo

    Abstract Mitochondria-associated membranes (MAMs) are essential communication subdomains of the endoplasmic reticulum (ER) that interact with mitochondria. We previously demonstrated that, upon macroautophagy/autophagy induction, AMBRA1 is recruited to the BECN1 complex and relocalizes to MAMs, where it regulates autophagy by interacting with raft-like components. ERLIN1 is an endoplasmic reticulum

  • Metformin rescues muscle function in BAG3 myofibrillar myopathy models
    Autophagy (IF 9.77) Pub Date : 2020-10-08
    Avnika A. Ruparelia; Emily A. McKaige; Caitlin Williams; Keith E. Schulze; Margit Fuchs; Viola Oorschot; Emmanuelle Lacene; Mirella Meregalli; Clara Lee; Rita J. Serrano; Emily C. Baxter; Keyne Monro; Yvan Torrente; Georg Ramm; Tanya Stojkovic; Josée N. Lavoie; Robert J. Bryson-Richardson

    Abstract Dominant de novo mutations in the co-chaperone BAG3 cause a severe form of myofibrillar myopathy, exhibiting progressive muscle weakness, muscle structural failure, and protein aggregation. To elucidate the mechanism of disease in, and identify therapies for, BAG3 myofibrillar myopathy, we generated two zebrafish models, one conditionally expressing BAG3P209L and one with a nonsense mutation

  • Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence
    Autophagy (IF 9.77) Pub Date : 2020-10-08
    Han Lu; Hui-Li Yang; Wen-Jie Zhou; Zhen-Zhen Lai; Xue-Min Qiu; Qiang Fu; Jian-Yuan Zhao; Jian Wang; Da-Jin Li; Ming-Qing Li

    ABSTRACT Deficiency in decidualization has been widely regarded as an important cause of spontaneous abortion. Generalized decidualization also includes massive infiltration and enrichment of NK cells. However, the underlying mechanism of decidual NK (dNK) cell residence remains largely unknown. Here, we observe that the increased macroautophagy/autophagy of decidual stromal cells (DSCs) during decidualization

  • Splicing variants of an endocytic regulator, BMP2K, differentially control autophagic degradation in erythroid cells
    Autophagy (IF 9.77) Pub Date : 2020-10-07
    Jaroslaw Cendrowski; Marta Miaczynska

    Splicing variants of an endocytic regulator, BMP2K, differentially control autophagic degradation in erythroid cells. Autophagy. Accepted 1 October 2020.

  • Membrane dynamics and protein targets of lipid droplet microautophagy during ER stress-induced proteostasis in the budding yeast, Saccharomyces cerevisiae
    Autophagy (IF 9.77) Pub Date : 2020-10-06
    Enrique J. Garcia; Pin-Chao Liao; Gary Tan; Jason D. Vevea; Cierra N. Sing; Catherine A. Tsang; J. Michael McCaffery; Istvan R. Boldogh; Liza A. Pon

    ABSTRACT Our previous studies reveal a mechanism for lipid droplet (LD)-mediated proteostasis in the endoplasmic reticulum (ER) whereby unfolded proteins that accumulate in the ER in response to lipid imbalance-induced ER stress are removed by LDs and degraded by microlipophagy (µLP), autophagosome-independent LD uptake into the vacuole (the yeast lysosome). Here, we show that dithiothreitol- or tunicamycin-induced

  • PRCC-TFE3 fusion-mediated PRKN/parkin-dependent mitophagy promotes cell survival and proliferation in PRCC-TFE3 translocation renal cell carcinoma
    Autophagy (IF 9.77) Pub Date : 2020-10-06
    Bo Wang; Xiaoqin Yin; Weidong Gan; Fan Pan; Shiyuan Li; Zou Xiang; Xiaodong Han; Dongmei Li

    ABSTRACT TFE3 (transcription factor binding to IGHM enhancer 3) nuclear translocation and transcriptional activity has been implicated in PINK1-PRKN/parkin-dependent mitophagy. However, the transcriptional control governing the mitophagy in TFE3/Xp11.2 translocation renal cell carcinoma (TFE3 tRCC) is largely unknown. Here, we investigated the role and mechanisms of PRCC-TFE3 fusion protein, one of

  • Secretory autophagy machinery and vesicular trafficking are involved in HMGB1 secretion
    Autophagy (IF 9.77) Pub Date : 2020-10-05
    Young Hun Kim; Man Sup Kwak; Bin Lee; Jae Min Shin; Sowon Aum; In Ho Park; Min Goo Lee; Jeon-Soo Shin

    ABSTRACT Nuclear protein HMGB1 is secreted in response to various stimuli and functions as a danger-associated molecular pattern. Extracellular HMGB1 induces inflammation, cytokine production, and immune cell recruitment via activation of various receptors. As HMGB1 does not contain an endoplasmic reticulum-targeting signal peptide, HMGB1 is secreted via the endoplasmic reticulum-Golgi independently

  • Essential role of autophagy in restricting poliovirus infection revealed by identification of an ATG7 defect in a poliomyelitis patient
    Autophagy (IF 9.77) Pub Date : 2020-10-05
    Nanna-Sophie Brinck Andersen; Sofie Eg Jørgensen; Kristian Alsbjerg Skipper; Simon Müller Larsen; Johanna Heinz; Michelle Mølgaard Thomsen; Ensieh Farahani; Yujia Cai; Alon Schneider Hait; Lise Kay; Jacob Giehm Mikkelsen; Mariane Høgsbjerg Schleimann; Martin Kristian Thomsen; Søren R. Paludan; Trine H. Mogensen

    Abstract Paralytic poliomyelitis is a rare disease manifestation following poliovirus (PV) infection. The disease determinants remain largely unknown. We used whole exome sequencing to uncover possible contributions of host genetics to the development of disease outcome in humans with poliomyelitis. We identified a patient with a variant in ATG7, an important regulatory gene in the macroautophagy/autophagy

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