AutophagyPub Date : 2024-04-01Epub Date: 2023-07-02DOI: 10.1080/15548627.2023.2230054
Anoshi Patel, Alex C Faesen
{"title":"Metamorphosis by ATG13 and ATG101 in human autophagy initiation.","authors":"Anoshi Patel, Alex C Faesen","doi":"10.1080/15548627.2023.2230054","DOIUrl":"10.1080/15548627.2023.2230054","url":null,"abstract":"<p><strong>Abbreviations: </strong>ATG, Autophagy-related, HORMA, protein domain named after HOP1-MAD2-REV7; RB1CC1, RB1 inducible coiled-coil 1; ULK, Unc-51-like kinase.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"968-969"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9742995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AutophagyPub Date : 2024-04-01Epub Date: 2023-04-17DOI: 10.1080/15548627.2023.2200627
Marianna Decet, Sandra-Fausia Soukup
{"title":"Endophilin-A/SH3GL2 calcium switch for synaptic autophagy induction is impaired by a Parkinson's risk variant.","authors":"Marianna Decet, Sandra-Fausia Soukup","doi":"10.1080/15548627.2023.2200627","DOIUrl":"10.1080/15548627.2023.2200627","url":null,"abstract":"<p><p>At the synapse, proteins are reused several times during neuronal activity, causing a decline in protein function over time. Although emerging evidence supports a role of autophagy in synaptic function, the precise molecular mechanisms linking neuronal activity, autophagy and synaptic dysfunction are vastly unknown. We show how extracellular calcium influx in the pre-synaptic terminal constitutes the initial stimulus for autophagosome formation in response to neuronal activity. This mechanism likely acts to rapidly support synaptic homeostasis and protein quality control when intense neuronal activity challenges the synaptic proteome. We identified a residue in the flexible region of EndoA (Endophilin A) that dictates calcium-dependent EndoA mobility from the plasma membrane to the cytosol, where this protein interacts with autophagic membranes to promote autophagosome formation. We discovered that a novel Parkinson's disease-risk mutation in SH3GL2 (SH3 domain containing GRB2 like 2, endophilin A1) disrupts the calcium sensing of SH3GL2, leading to an immobile protein that cannot respond to calcium influx and therefore disrupting autophagy induction at synapses. Our work shows how neuronal activity is connected with autophagy to maintain synaptic homeostasis and survival.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"925-927"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9303417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AutophagyPub Date : 2024-04-01Epub Date: 2023-06-12DOI: 10.1080/15548627.2023.2224206
Anais Franco-Romero, Jean Philippe Leduc-Gaudet, Sabah Na Hussain, Gilles Gouspillou, Marco Sandri
{"title":"PHAF1/MYTHO is a novel autophagy regulator that controls muscle integrity.","authors":"Anais Franco-Romero, Jean Philippe Leduc-Gaudet, Sabah Na Hussain, Gilles Gouspillou, Marco Sandri","doi":"10.1080/15548627.2023.2224206","DOIUrl":"10.1080/15548627.2023.2224206","url":null,"abstract":"<p><p>Skeletal muscles play key roles in movement, posture, thermogenesis, and whole-body metabolism. Autophagy plays essential roles in the regulation of muscle mass, function and integrity. However, the molecular machinery that regulates autophagy is still incompletely understood. In our recent study, we identified and characterized a novel Forkhead Box O (FoxO)-dependent gene, PHAF1/MYTHO (phagophore assembly factor 1/macro-autophagy and youth optimizer), as a novel autophagy regulator that controls muscle integrity. MYTHO/PHAF1 is upregulated in multiple conditions leading to muscle atrophy, and downregulation of its expression spares muscle atrophy triggered by fasting, denervation, cachexia and sepsis. Overexpression of PHAF1/MYTHO is sufficient to induce muscle atrophy. Prolonged downregulation of PHAF1/MYTHO causes a severe myopathic phenotype, which is characterized by impaired autophagy, muscle weakness, myofiber degeneration, mammalian target of rapamycin complex 1 (mTORC1) hyperactivation and extensive ultrastructural defects, such as accumulation of proteinaceous and membranous structures and tubular aggregates. This myopathic phenotype is attenuated upon administration of the mTORC1 inhibitor rapamycin. These findings position PHAF1/MYTHO as a novel regulator of skeletal muscle autophagy and tissue integrity.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"965-967"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FGF21 and autophagy coordinately counteract kidney disease progression during aging and obesity.","authors":"Satoshi Minami, Shinsuke Sakai, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Hiroaki Yonishi, Jun Nakamura, Shihomi Maeda, Sho Matsui, Isao Matsui, Yoshitaka Isaka","doi":"10.1080/15548627.2023.2259282","DOIUrl":"10.1080/15548627.2023.2259282","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) has reached epidemic proportions worldwide, partly due to the increasing population of elderly and obesity. Macroautophagy/autophagy counteracts CKD progression, whereas autophagy is stagnated owing to lysosomal overburden during aging and obesity, which promotes CKD progression. Therefore, for preventing CKD progression during aging and obesity, it is important to elucidate the compensation mechanisms of autophagy stagnation. We recently showed that FGF21 (fibroblast growth factor 21), which is a prolongevity and metabolic hormone, is induced by autophagy deficiency in kidney proximal tubular epithelial cells (PTECs); however, its pathophysiological role remains uncertain. Here, we investigated the interplay between FGF21 and autophagy and the direct contribution of endogenous FGF21 in the kidney during aging and obesity using PTEC-specific <i>fgf21</i>- and/or <i>atg5</i>-deficient mice at 24 months (<i>aged</i>) or under high-fat diet (<i>obese</i>) conditions. PTEC-specific FGF21 deficiency in <i>young</i> mice increased autophagic flux due to increased demand of autophagy, whereas <i>fgf21</i>-deficient <i>aged</i> or <i>obese</i> mice exacerbated autophagy stagnation due to severer lysosomal overburden caused by aberrant autophagy. FGF21 was robustly induced by autophagy deficiency, and <i>aged</i> or <i>obese</i> PTEC-specific <i>fgf21</i>- and <i>atg5</i>-double deficient mice deteriorated renal histology compared with <i>atg5</i>-deficient mice. Mitochondrial function was severely disturbed concomitant with exacerbated oxidative stress and downregulated TFAM (transcription factor A, mitochondrial) in double-deficient mice. These results indicate that FGF21 is robustly induced by autophagy disturbance and protects against CKD progression during aging and obesity by alleviating autophagy stagnation and maintaining mitochondrial homeostasis, which will pave the way to a novel treatment for CKD.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"489-504"},"PeriodicalIF":14.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10656878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AutophagyPub Date : 2024-02-21DOI: 10.1080/15548627.2024.2319022
Aida Rodríguez López, Lisa B. Frankel
{"title":"Selective degradation of ribosomes during oncogene-induced senescence: molecular insights and biological perspectives","authors":"Aida Rodríguez López, Lisa B. Frankel","doi":"10.1080/15548627.2024.2319022","DOIUrl":"https://doi.org/10.1080/15548627.2024.2319022","url":null,"abstract":"Ribosomes are conserved macromolecular machines that are responsible for protein synthesis in all cells. While our knowledge of ribosome biogenesis and function has increased significantly in recen...","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":"10 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling.","authors":"Mingyu Pan, Tongyu Hu, Jiao Lyu, Yue Yin, Jing Sun, Quanyi Wang, Lingxiao Xu, Haiyang Hu, Chen Wang","doi":"10.1080/15548627.2023.2256135","DOIUrl":"10.1080/15548627.2023.2256135","url":null,"abstract":"<p><p>STING1 (stimulator of interferon response cGAMP interactor 1) is the quintessential protein in the CGAS-STING1 signaling pathway, crucial for the induction of type I IFN (interferon) production and eliciting innate immunity. Nevertheless, the overactivation or sustained activation of STING1 has been closely associated with the onset of autoimmune disorders. Notably, the majority of these disorders manifest as an upregulated expression of type I interferons and IFN-stimulated genes (ISGs). Hence, strict regulation of STING1 activity is paramount to preserve immune homeostasis. Here, we reported that CSNK1A1/CK1α, a serine/threonine protein kinase, was essential to prevent the overactivation of STING1-mediated type I IFN signaling through autophagic degradation of STING1. Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation. Consistently, SSTC3, a selective CSNK1A1 agonist, significantly attenuated the response of the CGAS-STING1 signaling by promoting STING1 autophagic degradation. Importantly, pharmacological activation of CSNK1A1 using SSTC3 markedly repressed the systemic autoinflammatory responses in the <i>trex1</i><sup><i>-/-</i></sup> mouse autoimmune disease model and effectively suppressed the production of IFNs and ISGs in the PBMCs of SLE patients. Taken together, our study reveals a novel regulatory role of CSNK1A1 in the autophagic degradation of STING1 to maintain immune homeostasis. Manipulating CSNK1A1 through SSTC3 might be a potential therapeutic strategy for alleviating STING1-mediated aberrant type I IFNs in autoimmune diseases.<b>Abbreviations:</b> BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; HTDNA: herring testes DNA; IFIT1: interferon induced protein with tetratricopeptide repeats 1; IFNA4: interferon alpha 4; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; ISGs: IFN-stimulated genes; MEFs: mouse embryonic fibroblasts; PBMCs: peripheral blood mononuclear cells; RSAD2: radical S-adenosyl methionine domain containing 2; SLE: systemic lupus erythematosus; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"311-328"},"PeriodicalIF":14.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10813568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rhabdovirus encoded glycoprotein induces and harnesses host antiviral autophagy for maintaining its compatible infection.","authors":"Xiuqin Huang, Junkai Wang, Siping Chen, Siying Liu, Zhanbiao Li, Zhiyi Wang, Biao Chen, Chong Zhang, Yifei Zhang, Jinhui Wu, Xiaorong Yang, Qingjun Xie, Faqiang Li, Hong An, Jilei Huang, Huali Li, Chuanhe Liu, Xiaoxian Wu, Ding Xiang Liu, Xin Yang, Guohui Zhou, Tong Zhang","doi":"10.1080/15548627.2023.2252273","DOIUrl":"10.1080/15548627.2023.2252273","url":null,"abstract":"<p><p>Macroautophagy/autophagy has been recognized as a central antiviral defense mechanism in plant, which involves complex interactions between viral proteins and host factors. Rhabdoviruses are single-stranded RNA viruses, and the infection causes serious harm to public health, livestock, and crop production. However, little is known about the role of autophagy in the defense against rhabdovirus infection by plant. In this work, we showed that <i>Rice stripe mosaic cytorhabdovirus</i>(RSMV) activated autophagy in plants and that autophagy served as an indispensable defense mechanism during RSMV infection. We identified RSMV glycoprotein as an autophagy inducer that interacted with OsSnRK1B and promoted the kinase activity of OsSnRK1B on OsATG6b. RSMV glycoprotein was toxic to rice cells and its targeted degradation by OsATG6b-mediated autophagy was essential to restrict the viral titer in plants. Importantly, SnRK1-glycoprotein and ATG6-glycoprotein interactions were well-conserved between several other rhabdoviruses and plants. Together, our data support a model that SnRK1 senses rhabdovirus glycoprotein for autophagy initiation, while ATG6 mediates targeted degradation of viral glycoprotein. This conserved mechanism ensures compatible infection by limiting the toxicity of viral glycoprotein and restricting the infection of rhabdoviruses.<b>Abbreviations:</b> AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; ANOVA: analysis of variance; ATG: autophagy related; AZD: AZD8055; BiFC: bimolecular fluorescence complementation; BYSMV: barley yellow striate mosaic virus; Co-IP: co-immunoprecipitation; ConA: concanamycin A; CTD: C-terminal domain; DEX: dexamethasone; DMSO: dimethyl sulfoxide; G: glycoprotein; GFP: green fluorescent protein; MD: middle domain; MDC: monodansylcadaverine; NTD: N-terminal domain; OE: over expression; Os: <i>Oryza sativa</i>; PBS: phosphate-buffered saline; PtdIns3K: class III phosphatidylinositol-3-kinase; qRT-PCR: quantitative real-time reverse-transcription PCR; RFP: red fluorescent protein; RSMV: rice stripe mosaic virus; RSV: rice stripe virus; SGS3: suppressor of gene silencing 3; SnRK1: sucrose nonfermenting1-related protein kinase1; SYNV: sonchus yellow net virus; TEM: transmission electron microscopy; TM: transmembrane region; TOR: target of rapamycin; TRV: tobacco rattle virus; TYMaV: tomato yellow mottle-associated virus; VSV: vesicular stomatitis virus; WT: wild type; Y2H: yeast two-hybrid; YFP: yellow fluorescent protein.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"275-294"},"PeriodicalIF":14.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10813567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10577231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}