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  • MIR106A-5p upregulation suppresses autophagy and accelerates malignant phenotype in nasopharyngeal carcinoma
    Autophagy (IF 9.77) Pub Date : 2020-07-05
    Qingwen Zhu; Qicheng Zhang; Miao Gu; Kaiwen Zhang; Tian Xia; Siyu Zhang; Wenhui Chen; Haimeng Yin; Hui Yao; Yue Fan; Si Pan; Haijing Xie; Huiting Liu; Tianyi Cheng; Panpan Zhang; Ting Zhang; Bo You; Yiwen You

    ABSTRACT Dysregulated microRNAs (miRNAs) are involved in carcinoma progression, metastasis, and poor prognosis. We demonstrated that in nasopharyngeal carcinoma (NPC), transactivated MIR106A-5p promotes a malignant phenotype by functioning as a macroautophagy/autophagy suppressor by targeting BTG3 (BTG anti-proliferation factor 3) and activating autophagy-regulating MAPK signaling. MIR106A-5p expression

    更新日期:2020-07-05
  • Regulation and repurposing of nutrient sensing and autophagy in innate immunity
    Autophagy (IF 9.77) Pub Date : 2020-07-05
    Julia Sanchez-Garrido; Avinash R. Shenoy

    ABSTRACT Nutrients not only act as building blocks but also as signaling molecules. Nutrient-availability promotes cell growth and proliferation and suppresses catabolic processes, such as macroautophagy/autophagy. These effects are mediated by checkpoint kinases such as MTOR (mechanistic target of rapamycin kinase), which is activated by amino acids and growth factors, and AMP-activated protein kinase

    更新日期:2020-07-05
  • Selective autophagy inhibition through disruption of the PIK3C3-containing complex I
    Autophagy (IF 9.77) Pub Date : 2020-07-03
    I. Pavlinov; M. Salkovski; L.N. Aldrich

    The PIK3C3/VPS34-containing phosphatidylinositol 3-kinase (PtdIns3K) initiation complex (complex I) is necessary for macroautophagy/autophagy initiation and is comprised of PIK3R4/VPS15-PIK3C3/VPS34-BECN1-ATG14, while the endosomal trafficking complex (complex II) is necessary for vesicle trafficking and is comprised of PIK3R4/VPS15-PIK3C3/VPS34-BECN1-UVRAG. This composition difference was exploited

    更新日期:2020-07-05
  • The LC3-conjugation machinery specifies cargo loading and secretion of extracellular vesicles.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Elizabeth Delorme-Axford,Daniel J Klionsky

    ABSTRACT Classical macroautophagy/autophagy functions to maintain cell health during stressful conditions by targeting cytosolic components for degradation and recycling through the lysosomal pathway. In contrast, nondegradative secretory autophagy functions as an alternative autophagy mechanism to mediate extracellular secretion. A recent study published in Nature Cell Biology from the laboratory

    更新日期:2020-06-30
  • MLKL contributes to Western diet-induced liver injury through inhibiting autophagy.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Xiaoqin Wu,Laura E Nagy

    Macroautophagy/autophagy is critical in maintaining cellular functions and homeostasis. Dynamic regulation of autophagy is associated with development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH); however, the mechanisms involved in the regulation of autophagy in NAFLD/NASH are not well understood. Here we discuss our recent work identifying MLKL as an important

    更新日期:2020-06-30
  • A location, location, location mutation impairs DNM2-mediated release of nascent autophagosomes from recycling endosomes.
    Autophagy (IF 9.77) Pub Date : 2020-05-26
    Claudia Puri,David C Rubinsztein

    Elucidation of the membranes contributing to autophagosomes has been a critical question in the field, and an area of active research. Recently, we showed that key events in autophagosome formation, from PtdIns3P formation/WIPI2 recruitment to LC3-GABARAP membrane conjugation, occur on the RAB11A-positive compartment (recycling endosomes). This observation raised the question of how the LC3-positive

    更新日期:2020-06-30
  • Protein translocation into the ERGIC: an upstream event of secretory autophagy.
    Autophagy (IF 9.77) Pub Date : 2020-06-10
    Lei Liu,Min Zhang,Liang Ge

    Macroautophagy/autophagy was recently shown to regulate unconventional protein secretion through a process called secretory autophagy. How the secretory cargo selectively enters into the secretory autophagosome has been a central question. Our recent studies indicate that cargo translocation into the ER-Golgi intermediate compartment, a compartment contributing membranes to the forming autophagosome

    更新日期:2020-06-30
  • A RILP-regulated pathway coordinating autophagosome biogenesis with transport
    Autophagy (IF 9.77) Pub Date : 2020-06-28
    Noopur V. Khobrekar; Richard B. Vallee

    Mammalian cells, including neurons, use macroautophagy (here ‘autophagy’) to degrade damaged proteins and organelles, and recycle nutrients in response to starvation and other forms of cell stress. The basic cellular machinery responsible for autophagy is highly conserved from yeast to mammals. However, evidence for specific adaptations to more complex organisms and in highly differentiated cells (e

    更新日期:2020-06-29
  • AMPK is activated during lysosomal damage via a galectin-ubiquitin signal transduction system
    Autophagy (IF 9.77) Pub Date : 2020-06-28
    Jingyue Jia; Bhawana Bissa; Lukas Brecht; Lee Allers; Seong Won Choi; Yuexi Gu; Mark Zbinden; Mark R. Burge; Graham Timmins; Kenneth Hallows; Christian Behrends; Vojo Deretic

    Lysosomal damage activates AMPK, a regulator of macroautophagy/autophagy and metabolism, and elicits a strong ubiquitination response. Here we show that the cytosolic lectin LGALS9 detects lysosomal membrane breach by binding to lumenal glycoepitopes, and directs both the ubiquitination response and AMPK activation. Proteomic analyses have revealed increased LGALS9 association with lysosomes, and concomitant

    更新日期:2020-06-28
  • The Unfolded Protein Response Regulates Hepatic Autophagy by sXBP1-mediated Activation of TFEB
    Autophagy (IF 9.77) Pub Date : 2020-06-28
    Zeyuan Zhang; Qingwen Qian; Mark Li; Fan Shao; Wen-Xing Ding; Vitor A. Lira; Sophia X. Chen; Sara C. Sebag; Gökhan S. Hotamisligil; Huojun Cao; Ling Yang

    Defective macroautophagy/autophagy and a failure to initiate the adaptive unfolded protein response (UPR) in response to the endoplasmic reticulum (ER) stress contributes to obesity-associated metabolic dysfunction. However, whether and how unresolved ER stress leads to defects in the autophagy pathway and to the progression of obesity-associated hepatic pathologies remains unclear. Obesity suppresses

    更新日期:2020-06-28
  • Photodynamic therapy: autophagy and mitophagy, apoptosis and paraptosis
    Autophagy (IF 9.77) Pub Date : 2020-06-25
    David Kessel; John J. Reiners

    Macroautophagy/autophagy can play a cytoprotective role after photodynamic damage to malignant cells, depending on the site of subcellular damage initiated by reactive oxygen species. There is evidence for such protection when mitochondria are among the targets. Targeting lysosomes has been reported to be more effective for photokilling, perhaps because autophagy offers no cytoprotection. Photodynamic

    更新日期:2020-06-26
  • Regulating RIPK1: another way in which ULK1 contributes to survival
    Autophagy (IF 9.77) Pub Date : 2020-06-24
    Wenxian Wu; Björn Stork

    ABSTRACT The mammalian ULK1 is the central initiating kinase of bulk and selective macroautophagy/autophagy processes. In the past, both autophagy-relevant and non-autophagy-relevant substrates of this Ser/Thr kinase have been reported. Here, we describe our recent finding that ULK1 also regulates TNF signaling pathways. We find that inhibition of autophagy or specifically ULK1 increases TNF-induced

    更新日期:2020-06-24
  • Autophagy/virophagy: a “disposal strategy” to combat COVID-19
    Autophagy (IF 9.77) Pub Date : 2020-06-24
    Dalibor Mijaljica; Daniel J. Klionsky

    ABSTRACT Given the devastating consequences of the current COVID-19 pandemic and its impact on all of us, the question arises as to whether manipulating the cellular degradation (recycling, waste disposal) mechanism known as macroautophagy/autophagy (in particular, the selective degradation of virus particles, termed virophagy) might be a beneficial approach to fight the novel coronavirus, SARS-CoV-2

    更新日期:2020-06-24
  • Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability
    Autophagy (IF 9.77) Pub Date : 2020-06-23
    Eugènia Almacellas; Joffrey Pelletier; Charles Day; Santiago Ambrosio; Albert Tauler; Caroline Mauvezin

    ABSTRACT Lysosomes, as primary degradative organelles, are the endpoint of different converging pathways, including macroautophagy. To date, lysosome degradative function has been mainly studied in interphase cells, while their role during mitosis remains controversial. Mitosis dictates the faithful transmission of genetic material among generations, and perturbations of mitotic division lead to chromosomal

    更新日期:2020-06-23
  • Neutrophils use selective autophagy receptor Sqstm1/p62 to target Staphylococcus aureus for degradation in vivo in zebrafish.
    Autophagy (IF 9.77) Pub Date : 2020-06-19
    Josie F Gibson,Tomasz K Prajsnar,Christopher J Hill,Amy K Tooke,Justyna J Serba,Rebecca D Tonge,Simon J Foster,Andrew J Grierson,Philip W Ingham,Stephen A Renshaw,Simon A Johnston

    Macroautophagy/autophagy functions to degrade cellular components and intracellular pathogens. Autophagy receptors, including SQSTM1/p62, target intracellular pathogens. Staphylococcus aureus is a significant pathogen of humans, especially in immunocompromise. S. aureus may use neutrophils as a proliferative niche, but their intracellular fate following phagocytosis has not been analyzed in vivo. In

    更新日期:2020-06-22
  • Differential activation of eMI by distinct forms of cellular stress.
    Autophagy (IF 9.77) Pub Date : 2020-06-19
    Ana Mesquita,James Glenn,Andreas Jenny

    As one of the major, highly conserved catabolic pathways, autophagy delivers cytosolic components to lysosomes for degradation. It is essential for development, cellular homeostasis, and coping with stress. Reduced autophagy increases susceptibility to protein aggregation diseases and leads to phenotypes associated with aging. Of the three major forms of autophagy, macroautophagy (MA) can degrade organelles

    更新日期:2020-06-19
  • RETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1 -a dual organellar turnover mechanism.
    Autophagy (IF 9.77) Pub Date : 2020-06-19
    Debdatto Mookherjee,Subhrangshu Das,Rukmini Mukherjee,Manindra Bera,Swadhin Chandra Jana,Saikat Chakrabarti,Oishee Chakrabarti

    Turnover of cellular organelles, including endoplasmic reticulum (ER) and mitochondria, is orchestrated by an efficient cellular surveillance system. We have identified a mechanism for dual regulation of ER and mitochondria under stress. It is known that AMFR, an ER E3 ligase and ER-associated degradation (ERAD) regulator, degrades outer mitochondrial membrane (OMM) proteins, MFNs (mitofusins), via

    更新日期:2020-06-19
  • An autophagic deficit in the uterine vessel microenvironment provokes hyperpermeability through deregulated VEGFA, NOS1, and CTNNB1
    Autophagy (IF 9.77) Pub Date : 2020-06-17
    Bora Lee; Hyejin Shin; Ji-Eun Oh; Jaekyoung Park; Mira Park; Seung Chel Yang; Jin-Hyun Jun; Seok-Ho Hong; Haengseok Song; Hyunjung Jade Lim

    The uterus undergoes vascular changes during the reproductive cycle and pregnancy. Steroid hormone deprivation induces macroautophagy/autophagy in major uterine cell types. Herein, we explored the functions of uterine autophagy using the Amhr2-Cre-driven atg7 deletion model. Deletion of Atg7 was confirmed by functional deficit of autophagy in uterine stromal, myometrial, and vascular smooth muscle

    更新日期:2020-06-17
  • Eicosapentaenoic acid attenuates renal lipotoxicity by restoring autophagic flux.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Takeshi Yamamoto,Yoshitsugu Takabatake,Satoshi Minami,Shinsuke Sakai,Ryuta Fujimura,Atsushi Takahashi,Tomoko Namba-Hamano,Jun Matsuda,Tomonori Kimura,Isao Matsui,Jun-Ya Kaimori,Hiroaki Takeda,Masatomo Takahashi,Yoshihiro Izumi,Takeshi Bamba,Taiji Matsusaka,Fumio Niimura,Motoko Yanagita,Yoshitaka Isaka

    Recently, we identified a novel mechanism of lipotoxicity in the kidney proximal tubular cells (PTECs); lipid overload stimulates macroautophagy/autophagy for the renovation of plasma and organelle membranes to maintain the integrity of the PTECs. However, this autophagic activation places a burden on the lysosomal system, leading to a downstream suppression of autophagy, which manifests as phospholipid

    更新日期:2020-06-16
  • Phosphorylation of ULK1 serine 746 dictates ATG5-independent autophagy.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Xin Wen,Daniel J Klionsky

    There is a type of noncanonical autophagy, which is independent of ATG5 (autophagy related 5), also referred to as alternative autophagy. Both canonical and ATG5-independent alternative autophagy require the initiator ULK1 (unc-51 like kinase 1), but how ULK1 regulates these two types of autophagy differently remains unclear. A recent paper from Torii et al. demonstrates that phosphorylation of ULK1

    更新日期:2020-06-16
  • Scission, a critical step in autophagosome formation.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Yuchen Lei,Daniel J Klionsky

    A key feature of macroautophagy (hereafter autophagy) is the formation of the phagophore, a double-membrane compartment sequestering cargos and finally maturing into a vesicle termed an autophagosome; however, where these membranes originate from is not clear. In a previous study, researchers from the Rubinsztein lab proposed a model in which the autophagosome can evolve from the RAB11A-positive recycling

    更新日期:2020-06-16
  • Triethylenetetramine (trientine): a caloric restriction mimetic with a new mode of action.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Federico Pietrocola,Francesca Castoldi,Frank Madeo,Guido Kroemer

    Caloric restriction mimetics (CRMs) are nontoxic macroautophagy/autophagy enhancers that act through the stimulation of cytoplasmic protein deacetylation reactions. Thus far, three functional classes of CRMs have been described: inhibitors of acetyltransferases (such as spermidine), inhibitors of acetyl coenzyme (AcCoA) synthesis (such as hydroxycitrate) and activators of deacetylases/sirtuins (such

    更新日期:2020-06-16
  • PKD2/polycystin-2 induces autophagy by forming a complex with BECN1.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Daniel Peña-Oyarzun,Marcelo Rodriguez-Peña,Francesca Burgos-Bravo,Angelo Vergara,Catalina Kretschmar,Cristian Sotomayor-Flores,Cesar A Ramirez-Sarmiento,Humbert de Smedt,Montserrat Reyes,William Perez,Vicente A Torres,Eugenia Morselli,Francisco Altamirano,Christian A M Wilson,Joseph A Hill,Sergio Lavandero,Alfredo Criollo

    Macroautophagy/autophagy is an intracellular process involved in the breakdown of macromolecules and organelles. Recent studies have shown that PKD2/PC2/TRPP2 (polycystin 2, transient receptor potential cation channel), a non-selective cation channel permeable to Ca2+ that belongs to the family of transient receptor potential channels, is required for autophagy in multiple cell types by a mechanism

    更新日期:2020-06-16
  • LUBAC and OTULIN regulate autophagy initiation and maturation by mediating the linear ubiquitination and the stabilization of ATG13.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Yuanyuan Chu,Yingjin Kang,Cong Yan,Cuiwei Yang,Tao Zhang,Huanhuan Huo,Yanfen Liu

    Macroautophagy/autophagy is a membrane-mediated intracellular degradation pathway, through which bulky cytoplasmic content is digested in lysosomes. How the autophagy initiation and maturation steps are regulated is not clear. In this study, we found an E3 ubiquitin ligase complex, linear ubiquitin chain assembly complex (LUBAC) and a de-ubiquitinating enzyme (DUB) OTULIN localize to the phagophore

    更新日期:2020-06-16
  • Involvement of phosphorylation of ULK1 in alternative autophagy.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Satoru Torii,Shigeomi Shimizu

    Alternative autophagy is an ATG5 (autophagy related 5)-independent, Golgi membrane-derived form of macroautophagy. ULK1 (unc-51 like kinase 1) is an essential initiator not only for canonical autophagy but also for alternative autophagy. However, the mechanism as to how ULK1 differentially regulates both types of autophagy has remained unclear. Recently, we identified a novel phosphorylation site of

    更新日期:2020-06-16
  • Correction.
    Autophagy (IF 9.77) Pub Date : 2020-06-16

    (2020). Correction. Autophagy. Ahead of Print.

    更新日期:2020-06-16
  • Autophagy as an on-ramp to scientific discovery.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Casey Garr,Candyce M Sturgeon,Noah Franks,Veronica A Segarra

    The common view of art and science as polar opposites along the educational spectrum can sometimes mask the degree to which they inform one another. In fact, art can also serve as a way to foster interest in querying the natural world, ultimately allowing us to recruit highly creative individuals to join the scientific community. We have experienced firsthand how cellular processes, such as autophagy

    更新日期:2020-06-16
  • NRBF2 is a RAB7 effector required for autophagosome maturation and mediates the association of APP-CTFs with active form of RAB7 for degradation.
    Autophagy (IF 9.77) Pub Date : 2020-06-16
    Cui-Zan Cai,Chuanbin Yang,Xu-Xu Zhuang,Ning-Ning Yuan,Ming-Yue Wu,Jie-Qiong Tan,Ju-Xian Song,King-Ho Cheung,Huanxing Su,Yi-Tao Wang,Bei-Sha Tang,Christian Behrends,Siva Sundara Kumar Durairajan,Zhenyu Yue,Min Li,Jia-Hong Lu

    NRBF2 is a component of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex. Our previous study has revealed its role in regulating ATG14-associated PtdIns3K activity for autophagosome initiation. In this study, we revealed an unknown mechanism by which NRBF2 modulates autophagosome maturation and APP-C-terminal fragment (CTF) degradation. Our data showed that NRBF2 localized at autolysosomes

    更新日期:2020-06-16
  • Autophagy as an emerging target for COVID-19: lessons from an old friend, chloroquine.
    Autophagy (IF 9.77) Pub Date : 2020-06-10
    Srinivasa Reddy Bonam,Sylviane Muller,Jagadeesh Bayry,Daniel J Klionsky

    Abstract During the last week of December 2019, Wuhan (China) was confronted with the first case of respiratory tract disease 2019 (coronavirus disease 2019, COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the rapid outbreak of the transmission (~3.64 million positive cases and high mortality as of May 5, 2020), the world is looking for immediate and better

    更新日期:2020-06-10
  • Open questions for harnessing autophagy-modulating drugs in the SARS-CoV-2 war: hope or hype?
    Autophagy (IF 9.77) Pub Date : 2020-06-10
    Patrick Brest,Jonathan Benzaquen,Daniel J Klionsky,Paul Hofman,Baharia Mograbi

    At a time when the world faces an emotional breakdown, crushing our dreams, if not, taking our lives, we realize that together we must fight the war against the COVID-19 outbreak even if almost the majority of the scientific community finds itself confined at home. Every day, we, scientists, listen to the latest news with its promises and announcements. Across the world, a surge of clinical trials

    更新日期:2020-06-10
  • The C9orf72-SMCR8-WDR41 complex is a GAP for small GTPases.
    Autophagy (IF 9.77) Pub Date : 2020-06-10
    Dan Tang,Jingwen Sheng,Liangting Xu,Chuangye Yan,Shiqian Qi

    Massive expansions of the hexanucleotide in C9orf72 are the primary genetic origins of familial amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). Current studies have found that this repeat sequence participates in the disease process by producing neurotoxic substances and reducing the level of C9orf72 protein; however, the progress in the functional study of C9orf72 is slow

    更新日期:2020-06-10
  • MERIT, a cellular system coordinating lysosomal repair, removal and replacement.
    Autophagy (IF 9.77) Pub Date : 2020-06-10
    Jingyue Jia,Aurore Claude-Taupin,Yuexi Gu,Seong Won Choi,Ryan Peters,Bhawana Bissa,Michal H Mudd,Lee Allers,Sandeep Pallikkuth,Keith A Lidke,Michelle Salemi,Brett Phinney,Muriel Mari,Fulvio Reggiori,Vojo Deretic

    Membrane integrity is essential for cellular survival and function. The spectrum of mechanisms protecting cellular and intracellular membranes is not fully known. Our recent work has uncovered a cellular system termed MERIT for lysosomal membrane repair, removal and replacement. Specifically, lysosomal membrane damage induces, in succession, ESCRT-dependent membrane repair, macroautophagy/autophagy-dominant

    更新日期:2020-06-10
  • Live imaging of intra-lysosome pH in cell lines and primary neuronal culture using a novel genetically encoded biosensor.
    Autophagy (IF 9.77) Pub Date : 2020-06-09
    Amy H Ponsford,Thomas A Ryan,Andrea Raimondi,Emanuele Cocucci,Susanne A Wycislo,Florian Fröhlich,Laura E Swan,Massimiliano Stagi

    ABSTRACT Disorders of lysosomal physiology have increasingly been found to underlie the pathology of a rapidly growing cast of neurodevelopmental disorders and sporadic diseases of aging. One cardinal aspect of lysosomal (dys)function is lysosomal acidification in which defects trigger lysosomal stress signaling and defects in proteolytic capacity. We have developed a genetically encoded ratiometric

    更新日期:2020-06-09
  • Atg21 organizes Atg8 lipidation at the contact of the vacuole with the phagophore.
    Autophagy (IF 9.77) Pub Date : 2020-06-09
    Lena Munzel,Piotr Neumann,Florian B Otto,Roswitha Krick,Janina Metje-Sprink,Benjamin Kroppen,Narain Karedla,Jörg Enderlein,Michael Meinecke,Ralf Ficner,Michael Thumm

    Coupling of Atg8 to phosphatidylethanolamine is crucial for the expansion of the crescent-shaped phagophore during cargo engulfment. Atg21, a PtdIns3P-binding beta-propeller protein, scaffolds Atg8 and its E3-like complex Atg12–Atg5-Atg16 during lipidation. The crystal structure of Atg21, in complex with the Atg16 coiled-coil domain, showed its binding at the bottom side of the Atg21 beta-propeller

    更新日期:2020-06-09
  • Vac8 determines phagophore assembly site vacuolar localization during nitrogen starvation-induced autophagy.
    Autophagy (IF 9.77) Pub Date : 2020-06-08
    Damian Gatica,Xin Wen,Heesun Cheong,Daniel J Klionsky

    Macroautophagy/autophagy is a key catabolic process in which different cellular components are sequestered inside double-membrane vesicles called autophagosomes for subsequent degradation. In yeast, autophagosome formation occurs at the phagophore assembly site (PAS), a specific perivacuolar location that works as an organizing center for the recruitment of different autophagy-related (Atg) proteins

    更新日期:2020-06-08
  • Streptococcus pneumoniae promotes its own survival via choline-binding protein CbpC-mediated degradation of ATG14.
    Autophagy (IF 9.77) Pub Date : 2020-06-08
    Sayaka Shizukuishi,Michinaga Ogawa,Akihide Ryo,Makoto Ohnishi

    Streptococcus pneumoniae is an opportunistic bacterial pathogen that can promote severe infection by overcoming the epithelial and blood-brain barrier. Pneumococcal cell-surface virulence factors, including cell wall-anchored choline-binding proteins (Cbps) play pivotal roles in promoting invasive disease. We reported previously that intracellular pneumococci were detected by hierarchical macroautophagic/autophagic

    更新日期:2020-06-08
  • Puncta intended: connecting the dots between autophagy and cell stress networks.
    Autophagy (IF 9.77) Pub Date : 2020-06-07
    Cally J Ho,Gayathri Samarasekera,Katharina Rothe,Jing Xu,Kevin C Yang,Emily Leung,Michelle Chan,Xiaoyan Jiang,Sharon M Gorski

    Proteome profiling and global protein-interaction approaches have significantly improved our knowledge of the protein interactomes of autophagy and other cellular stress-response pathways. New discoveries regarding protein complexes, interaction partners, interaction domains, and biological roles of players that are part of these pathways are emerging. The fourth Vancouver Autophagy Symposium showcased

    更新日期:2020-06-07
  • Autophagy coupled to translation is required for long-term memory.
    Autophagy (IF 9.77) Pub Date : 2020-06-05
    Kiran Pandey,Xiao-Wen Yu,Adam Steinmetz,Cristina M Alberini

    An increase in protein synthesis following learning is a fundamental and evolutionarily conserved mechanism of long-term memory. To maintain homeostasis, this protein synthesis must be counterbalanced by mechanisms such as protein degradation. Recent studies reported that macroautophagy/autophagy, a major protein degradation mechanism, is required for long-term memory formation. However, how learning

    更新日期:2020-06-05
  • Using Reactome to build an autophagy mechanism knowledgebase.
    Autophagy (IF 9.77) Pub Date : 2020-06-02
    Thawfeek Mohamed Varusai,Steven Jupe,Cristoffer Sevilla,Lisa Matthews,Marc Gillespie,Lincoln Stein,Guanming Wu,Peter D'Eustachio,Emmanouil Metzakopian,Henning Hermjakob

    ABSTRACT The 21st century has revealed much about the fundamental cellular process of autophagy. Autophagy controls the catabolism and recycling of various cellular components both as a constitutive process and as a response to stress and foreign material invasion. There is considerable knowledge of the molecular mechanisms of autophagy, and this is still growing as new modalities emerge. There is

    更新日期:2020-06-02
  • Corrigendum.
    Autophagy (IF 9.77) Pub Date : 2020-05-31

    (2020). Corrigendum. Autophagy. Ahead of Print.

    更新日期:2020-05-31
  • Selective autophagy controls the stability of transcription factor IRF3 to balance type I interferon production and immune suppression.
    Autophagy (IF 9.77) Pub Date : 2020-05-31
    Yaoxing Wu,Shouheng Jin,Qingxiang Liu,Yu Zhang,Ling Ma,Zhiyao Zhao,Shuai Yang,Yi-Ping Li,Jun Cui

    IRF3 (interferon regulatory factor 3) is one of the most critical transcription factors in antiviral innate immune signaling, which is ubiquitously expressed in a variety of cells. Although it has been demonstrated that IRF3 can provoke multiple cellular processes during viral infection, including type I interferon (IFN) production, the mechanisms underlying the precise regulation of IRF3 activity

    更新日期:2020-05-31
  • TNFAIP8L2/TIPE2 impairs autolysosome reformation via modulating the RAC1-MTORC1 axis.
    Autophagy (IF 9.77) Pub Date : 2020-05-28
    Wen Li,Yulan Li,Yetong Guan,Yingxin Du,Mingsheng Zhao,Xiaotong Chen,Faliang Zhu,Chun Guo,Yufeng Jia,Yuan Li,Xiaoyu Wang,Xiaoyan Wang,Yongyu Shi,Qun Wang,Yan Li,Lining Zhang

    Macroautophagy/autophagy is an evolutionarily conserved process that involves the selective degradation of cytoplasmic components within lysosomes in response to starvation. Autophagy is an ancient defense mechanism that has been closely integrated with the immune system and has multiple effects on innate and adaptive immunity. The pro-inflammatory and anti-inflammatory cytokines can activate and inhibit

    更新日期:2020-05-28
  • Selective autophagy of MHC-I promotes immune evasion of pancreatic cancer.
    Autophagy (IF 9.77) Pub Date : 2020-05-27
    Keisuke Yamamoto,Anthony Venida,Rushika M Perera,Alec C Kimmelman

    Major histocompatibility complex class I (MHC-I) is a key molecule in anti-tumor adaptive immunity. MHC-I is essential for endogenous antigen presentation by cancer cells and subsequent recognition and clearance by CD8+ T cells. Defects in MHC-I expression occur frequently in several cancers, leading to impaired antigen presentation, immune evasion and/or resistance to immune checkpoint blockade (ICB)

    更新日期:2020-05-27
  • High-throughput screening of functional deubiquitinating enzymes in autophagy.
    Autophagy (IF 9.77) Pub Date : 2020-05-26
    Shuo Tian,Shouheng Jin,Yaoxing Wu,Tao Liu,Man Luo,Jiayu Ou,Weihong Xie,Jun Cui

    Macroautophagy/autophagy, a eukaryotic homeostatic process that sequesters cytoplasmic constituents for lysosomal degradation, is orchestrated by a number of autophagy-related (ATG) proteins tightly controlled by post-translational modifications. However, the involvement of reversible ubiquitination in the regulation of autophagy remains largely unclear. Here, we performed a single-guide RNA-based

    更新日期:2020-05-26
  • Synucleinphagy: a microglial "community cleanup program" for neuroprotection.
    Autophagy (IF 9.77) Pub Date : 2020-05-26
    Insup Choi,Steven P Seegobin,Dongxiao Liang,Zhenyu Yue

    SNCA/α-synuclein is a major component in the Lewy body (LB), a pathological hallmark of Parkinson disease (PD) and dementia with Lewy body (DLB), collectively known as synucleinopathies. SNCA/α-synuclein can be secreted from neurons and transmitted to neighboring cells including neurons and glia, which underlie the spreading of LB pathology as described by Braak and colleagues. We recently have investigated

    更新日期:2020-05-26
  • Autophagy and post-ischemic conditioning in retinal ischemia.
    Autophagy (IF 9.77) Pub Date : 2020-05-26
    Biji Mathew,Mohansrinivas Chennakesavalu,Monica Sharma,Leianne A Torres,Clara R Stelman,Sophie Tran,Raj Patel,Nathan Burg,Maryna Salkovski,Konrad Kadzielawa,Figen Seiler,Leslie N Aldrich,Steven Roth

    Retinal ischemia is a major cause of vision loss and a common underlying mechanism associated with diseases, such as diabetic retinopathy and central retinal artery occlusion. We have previously demonstrated the robust neuroprotection in retina induced by post-conditioning (post-C), a brief period of ischemia, 24 h, following a prolonged and damaging initial ischemia. The mechanisms underlying post-C-mediated

    更新日期:2020-05-26
  • Restoration of CTSD (cathepsin D) and lysosomal function in stroke is neuroprotective.
    Autophagy (IF 9.77) Pub Date : 2020-05-25
    M Iqbal Hossain,Joshua M Marcus,Jun Hee Lee,Patrick L Garcia,VinodKumar Singh,John J Shacka,Jianhua Zhang,Toby I Gropen,Charles N Falany,Shaida A Andrabi

    Stroke is a leading cause of death and disability. The pathophysiological mechanisms associated with stroke are very complex and not fully understood. Lysosomal function has a vital physiological function in the maintenance of cellular homeostasis. In neurons, CTSD (cathepsin D) is an essential protease involved in the regulation of proteolytic activity of the lysosomes. Loss of CTSD leads to lysosomal

    更新日期:2020-05-25
  • New tricks of an old autophagy regulator: AMPK-dependent regulation of autophagy through CCNY (cyclin Y)-CDK16.
    Autophagy (IF 9.77) Pub Date : 2020-06-01
    Damián Gatica,Daniel J Klionsky

    AMPK is one of the main regulators of energy homeostasis in the cell, achieving this role in part by upregulating autophagy in times of nutrient deprivation. Previous reports have described several AMPK substrates involved in autophagy regulation; however, there are still undiscovered AMPK downstream effectors that could play an important role in autophagy. In a new article, Dohmen et al. discovered

    更新日期:2020-05-22
  • LC3-associated phagocytosis in myeloid cells, a fireman that restrains inflammation and liver fibrosis, via immunoreceptor inhibitory signaling.
    Autophagy (IF 9.77) Pub Date : 2020-05-21
    JingHong Wan,Emmanuel Weiss,Sanae Ben Mkaddem,Morgane Mabire,Pierre-Marie Choinier,Tristan Thibault-Sogorb,Pushpa Hegde,Marcelle Bens,Linda Broer,Hélène Gilgenkrantz,Richard Moreau,Loredana Saveanu,Patrice Codogno,Renato C Monteiro,Sophie Lotersztajn

    Control of systemic and hepatic inflammation, in particular originating from monocytes/macrophages, is crucial to prevent liver fibrosis and its progression to end-stage cirrhosis. LC3-associated phagocytosis (LAP) is a non-canonical form of autophagy that shifts the monocyte/macrophage phenotype to an anti-inflammatory phenotype. In a recent study, we uncovered LAP as a protective mechanism against

    更新日期:2020-05-21
  • Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.
    Autophagy (IF 9.77) Pub Date : 2020-05-20
    Zu-Guo Zheng,Si-Tong Zhu,Hui-Min Cheng,Xin Zhang,Gang Cheng,Pyone Myat Thu,Supeng Perry Wang,Hui-Jun Li,Ming Ding,Lei Qiang,Xiao-Wei Chen,Qing Zhong,Ping Li,Xiaojun Xu

    SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated

    更新日期:2020-05-20
  • Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway
    Autophagy (IF 9.77) Pub Date : 2020-05-20
    Zu-Guo Zheng; Si-Tong Zhu; Hui-Min Cheng; Xin Zhang; Gang Cheng; Pyone Myat Thu; Supeng Perry Wang; Hui-Jun Li; Ming Ding; Lei Qiang; Xiao-Wei Chen; Qing Zhong; Ping Li; Xiaojun Xu

    SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated

    更新日期:2020-05-20
  • Regulation of autophagy by DNA G-quadruplexes.
    Autophagy (IF 9.77) Pub Date : 2020-05-18
    Pauline Lejault,Jose F Moruno-Manchon,Sree M Vemu,Pedram Honarpisheh,Liang Zhu,Nayun Kim,Akihiko Urayama,David Monchaud,Louise D McCullough,Andrey S Tsvetkov

    Guanine-rich DNA strands can form secondary structures known as G-quadruplexes (G4-DNA). G4-DNA is important for the regulation of replication and transcription. We recently showed that the expression of Atg7, a gene that is critical for macroautophagy/autophagy, is controlled by G4-DNA in neurons. We demonstrated that the transcription factor SUB1/PC4 and the G4-DNA-specific antibody HF2 bind to a

    更新日期:2020-05-18
  • BHRF1, a BCL2 viral homolog, disturbs mitochondrial dynamics and stimulates mitophagy to dampen type I IFN induction.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Géraldine Vilmen,Damien Glon,Gabriel Siracusano,Marion Lussignol,Zhouwulin Shao,Eva Hernandez,Daniel Perdiz,Frédérique Quignon,Lina Mouna,Christian Poüs,Henri Gruffat,Vincent Maréchal,Audrey Esclatine

    Mitochondria respond to many cellular functions and act as central hubs in innate immunity against viruses. This response is notably due to their role in the activation of interferon (IFN) signaling pathways through the activity of MAVS (mitochondrial antiviral signaling protein) present at the mitochondrial surface. Here, we report that the BHRF1 protein, a BCL2 homolog encoded by Epstein-Barr virus

    更新日期:2020-05-13
  • CYBB/NOX2 in conventional DCs controls T cell encephalitogenicity during neuroinflammation.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Christian W Keller,Monika B Kotur,Sarah Mundt,Nikolaos Dokalis,Laure-Anne Ligeon,Ajay M Shah,Marco Prinz,Burkhard Becher,Christian Münz,Jan D Lünemann

    Whereas central nervous system (CNS) homeostasis is highly dependent on tissue surveillance by immune cells, dysregulated entry of leukocytes during autoimmune neuroinflammation causes severe immunopathology and neurological deficits. To invade the CNS parenchyma, encephalitogenic T helper (TH) cells must encounter their cognate antigen(s) presented by local major histocompatibility complex (MHC) class

    更新日期:2020-05-13
  • Autophagy in the physiological endometrium and cancer.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Laura Devis-Jauregui,Núria Eritja,Meredith Leigh Davis,Xavier Matias-Guiu,David Llobet-Navàs

    Autophagy is a highly conserved catabolic process and a major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles. An increasing body of evidence has unveiled autophagy as an indispensable biological function that helps to maintain normal tissue homeostasis and metabolic fitness that can also lead to severe consequences for the normal cellular functioning when altered

    更新日期:2020-05-13
  • New tricks of an old autophagy regulator: AMPK-dependent regulation of autophagy through CCNY (cyclin Y)-CDK16
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Damián Gatica; Daniel J. Klionsky

    ABSTRACT AMPK is one of the main regulators of energy homeostasis in the cell, achieving this role in part by upregulating autophagy in times of nutrient deprivation. Previous reports have described several AMPK substrates involved in autophagy regulation; however, there are still undiscovered AMPK downstream effectors that could play an important role in autophagy. In a new article, Dohmen et al.

    更新日期:2020-05-13
  • Mitophagy deficiency increases NLRP3 to induce brown fat dysfunction in mice.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Myoung Seok Ko,Ji Young Yun,In-Jeoung Baek,Jung Eun Jang,Jung Jin Hwang,Seung Eun Lee,Seung-Ho Heo,David A Bader,Chul-Ho Lee,Jaeseok Han,Jong-Seok Moon,Jae Man Lee,Eun-Gyoung Hong,In-Kyu Lee,Seong Who Kim,Joong Yeol Park,Sean M Hartig,Un Jung Kang,David D Moore,Eun Hee Koh,Ki-Up Lee

    Although macroautophagy/autophagy deficiency causes degenerative diseases, the deletion of essential autophagy genes in adipocytes paradoxically reduces body weight. Brown adipose tissue (BAT) plays an important role in body weight regulation and metabolic control. However, the key cellular mechanisms that maintain BAT function remain poorly understood. in this study, we showed that global or brown

    更新日期:2020-05-13
  • An integrative multi-omics approach uncovers the regulatory role of CDK7 and CDK4 in autophagy activation induced by silica nanoparticles.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Chen Ruan,Chenwei Wang,Xuanqing Gong,Ying Zhang,Wankun Deng,Jiaqi Zhou,Dengtong Huang,Zining Wang,Qiong Zhang,Anyuan Guo,Jiahong Lu,Jinhao Gao,Di Peng,Yu Xue

    Dysfunction of macroautophagy/autophagy has been postulated as a major cellular toxicological response to nanomaterials. It has been reported that excessive autophagy activation, induced by silica nanoparticles (SiNPs), contributes to autophagy dysfunction, whereas little is known how SiNPs trigger autophagy activation. Here, we treated normal rat kidney (NRK) cells using 3 different sizes of SiNPs

    更新日期:2020-05-13
  • Involvement of CASP9 (caspase 9) in IGF2R/CI-MPR endosomal transport.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Jie Han,Leslie A Goldstein,Wen Hou,Simon C Watkins,Hannah Rabinowich

    Recently, we reported that increased expression of CASP9 pro-domain, at the endosomal membrane in response to HSP90 inhibition, mediates a cell-protective effect that does not involve CASP9 apoptotic activity. We report here that a non-apoptotic activity of endosomal membrane CASP9 facilitates the retrograde transport of IGF2R/CI-MPR from the endosomes to the trans-Golgi network, indicating the involvement

    更新日期:2020-05-13
  • The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells.
    Autophagy (IF 9.77) Pub Date : 2020-05-13
    Pau Muñoz-Guardiola,Josefina Casas,Elisabet Megías-Roda,Sònia Solé,Héctor Perez-Montoyo,Marc Yeste-Velasco,Tatiana Erazo,Nora Diéguez-Martínez,Sergio Espinosa-Gil,Cristina Muñoz-Pinedo,Guillermo Yoldi,Jose L Abad,Miguel F Segura,Teresa Moran,Margarita Romeo,Joaquim Bosch-Barrera,Ana Oaknin,Jose Alfón,Carles Domènech,Gemma Fabriàs,Guillermo Velasco,Jose M Lizcano

    ABTL0812 is a first-in-class small molecule with anti-cancer activity, which is currently in clinical evaluation in a phase 2 trial in patients with advanced endometrial and squamous non-small cell lung carcinoma (NCT03366480). Previously, we showed that ABTL0812 induces TRIB3 pseudokinase expression, resulting in the inhibition of the AKT-MTORC1 axis and macroautophagy/autophagy-mediated cancer cell

    更新日期:2020-05-13
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