{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:50:50Z","timestamp":1790805050987,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91854115, 31970044, 31771571"],"award-info":[{"award-number":["91854115, 31970044, 31771571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autophagy is an evolutionarily conserved pathway, in which cytoplasmic components are sequestered within double-membrane vesicles called autophagosomes and then transported into lysosomes or vacuoles for degradation. Over 40 conserved autophagy-related (ATG) genes define the core machinery for the five processes of autophagy: initiation, nucleation, elongation, closure, and fusion. In this review, we focus on one of the least well-characterized events in autophagy, namely the closure of the isolation membrane\/phagophore to form the sealed autophagosome. This process is tightly regulated by ESCRT machinery, ATG proteins, Rab GTPase and Rab-related proteins, SNAREs, sphingomyelin, and calcium. We summarize recent progress in the regulation of autophagosome closure and discuss the key questions remaining to be addressed.<\/jats:p>","DOI":"10.3390\/cells10112814","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:29:46Z","timestamp":1634765386000},"page":"2814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Key Regulators of Autophagosome Closure"],"prefix":"10.3390","volume":"10","author":[{"given":"Wenyan","family":"Jiang","sequence":"first","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Faculty of Environment and Life Sciences, Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechai","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Faculty of Environment and Life Sciences, Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuicui","family":"Ji","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Faculty of Environment and Life Sciences, Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Faculty of Environment and Life Sciences, Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Song","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Faculty of Environment and Life Sciences, Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory for Marine Fisheries and Aquaculture, Qingdao National Laboratory for Marine Science and Technology, Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Faculty of Environment and Life Sciences, Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nrm2708","article-title":"Dynamics and diversity in autophagy mechanisms: Lessons from yeast","volume":"10","author":"Nakatogawa","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrm3696","article-title":"The autophagosome: Origins unknown, biogenesis complex","volume":"14","author":"Lamb","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/cr.2013.168","article-title":"The machinery of macroautophagy","volume":"24","author":"Feng","year":"2014","journal-title":"Cell Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/ncb0910-814","article-title":"Eaten alive: A history of macroautophagy","volume":"12","author":"Yang","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","article-title":"Mechanism and medical implications of mammalian autophagy","volume":"19","author":"Dikic","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological Functions of Autophagy Genes: A Disease Perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.1074\/jbc.R117.810366","article-title":"A molecular perspective of mammalian autophagosome biogenesis","volume":"293","author":"Mercer","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1080\/15548627.2015.1091552","article-title":"Autophagosome closure requires membrane scission","volume":"11","author":"Knorr","year":"2015","journal-title":"Autophagy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.devcel.2011.05.015","article-title":"The ESCRT pathway","volume":"21","author":"Henne","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41580-019-0177-4","article-title":"The many functions of ESCRTs","volume":"21","author":"Vietri","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1083\/jcb.200702115","article-title":"Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease","volume":"179","author":"Filimonenko","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.cub.2007.07.029","article-title":"ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration","volume":"17","author":"Lee","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/j.cub.2007.09.032","article-title":"ESCRTs and Fab1 regulate distinct steps of autophagy","volume":"17","author":"Rusten","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1247\/csf.27.29","article-title":"SKD1 AAA ATPase-dependent endosomal transport is involved in autolysosome formation","volume":"27","author":"Nara","year":"2002","journal-title":"Cell Struct. Funct."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1247\/csf.22.501","article-title":"Mutational analysis of Csc1\/Vps4p: Involvement of endosome in regulation of autophagy in yeast","volume":"22","author":"Shirahama","year":"1997","journal-title":"Cell Struct. Funct."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1038\/s41467-018-05254-w","article-title":"An autophagy assay reveals the ESCRT-III component CHMP2A as a regulator of phagophore closure","volume":"9","author":"Takahashi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.1083\/jcb.201902170","article-title":"VPS37A directs ESCRT recruitment for phagophore closure","volume":"218","author":"Takahashi","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1080\/15548627.2019.1639301","article-title":"ESCRT-mediated phagophore sealing during mitophagy","volume":"16","author":"Zhen","year":"2020","journal-title":"Autophagy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1083\/jcb.201811173","article-title":"Rab5-dependent autophagosome closure by ESCRT","volume":"218","author":"Zhou","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1080\/15548627.2019.1628547","article-title":"Autophagosome closure by ESCRT: Vps21\/RAB5-regulated ESCRT recruitment via an Atg17-Snf7 interaction","volume":"15","author":"Zhou","year":"2019","journal-title":"Autophagy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4762","DOI":"10.1091\/mbc.e08-03-0309","article-title":"The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice","volume":"19","author":"Sou","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1091\/mbc.e08-03-0312","article-title":"An Atg4B mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure","volume":"19","author":"Fujita","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1038\/emboj.2010.74","article-title":"LC3 and GATE-16\/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis","volume":"29","author":"Weidberg","year":"2010","journal-title":"EMBO J."},{"key":"ref_24","first-page":"4089","article-title":"Ultrastructural analysis of autophagosome organization using mammalian autophagy-deficient cells","volume":"127","author":"Itakura","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1128\/MCB.01327-13","article-title":"A cluster of thin tubular structures mediates transformation of the endoplasmic reticulum to autophagic isolation membrane","volume":"34","author":"Uemura","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e48412","DOI":"10.15252\/embr.201948412","article-title":"A conserved ATG2-GABARAP family interaction is critical for phagophore formation","volume":"21","author":"Bozic","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1091\/mbc.e11-09-0785","article-title":"Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets","volume":"23","author":"Velikkakath","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30442","DOI":"10.1074\/jbc.M102342200","article-title":"Apg2 is a novel protein required for the cytoplasm to vacuole targeting, autophagy, and pexophagy pathways","volume":"276","author":"Wang","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhou, F., Zou, S., Chen, Y., Lipatova, Z., Sun, D., Zhu, X., Li, R., Wu, Z., You, W., and Cong, X. (2017). A Rab5 GTPase module is important for autophagosome closure. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1007020"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.molcel.2013.08.041","article-title":"Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation","volume":"52","author":"Lu","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/tra.12640","article-title":"TRAPPC11 functions in autophagy by recruiting ATG2B-WIPI4\/WDR45 to preautophagosomal membranes","volume":"20","author":"Stanga","year":"2019","journal-title":"Traffic"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3389\/fcell.2020.00460","article-title":"Casein Kinase 1 Family Member CK1delta\/Hrr25 Is Required for Autophagosome Completion","volume":"8","author":"Li","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1080\/15548627.2016.1159378","article-title":"Excess sphingomyelin disturbs ATG9A trafficking and autophagosome closure","volume":"12","author":"Vindelov","year":"2016","journal-title":"Autophagy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.4161\/auto.25900","article-title":"Modulation of intracellular calcium homeostasis blocks autophagosome formation","volume":"9","author":"Engedal","year":"2013","journal-title":"Autophagy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/tra.12805","article-title":"The ESCRT-III complex contributes to macromitophagy in yeast","volume":"22","author":"Wu","year":"2021","journal-title":"Traffic"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1083\/jcb.151.2.263","article-title":"The reversible modification regulates the membrane-binding state of Apg8\/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway","volume":"151","author":"Kirisako","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"51841","DOI":"10.1074\/jbc.M308762200","article-title":"A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L","volume":"278","author":"Hemelaar","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"37298","DOI":"10.1074\/jbc.C700195200","article-title":"The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy","volume":"282","author":"Hanada","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.devcel.2007.04.005","article-title":"Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle","volume":"12","author":"Cai","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1146\/annurev-biochem-052810-093700","article-title":"GTPase networks in membrane traffic","volume":"81","author":"Novick","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nrm2002","article-title":"SNAREs\u2014Engines for membrane fusion","volume":"7","author":"Jahn","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15781","DOI":"10.1073\/pnas.95.26.15781","article-title":"Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs","volume":"95","author":"Fasshauer","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nrm2417","article-title":"Mechanisms of membrane fusion: Disparate players and common principles","volume":"9","author":"Martens","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"119064","DOI":"10.1016\/j.bbamcr.2021.119064","article-title":"Small but mighty: Atg8s and Rabs in membrane dynamics during autophagy","volume":"1868","author":"Barz","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.4161\/auto.29395","article-title":"The autophagic roles of Rab small GTPases and their upstream regulators: A review","volume":"10","author":"Szatmari","year":"2014","journal-title":"Autophagy"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.semcdb.2016.07.009","article-title":"SNARE-mediated membrane fusion in autophagy","volume":"60","author":"Wang","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/mp.2009.152","article-title":"The dysbindin-containing complex (BLOC-1) in brain: Developmental regulation, interaction with SNARE proteins and role in neurite outgrowth","volume":"15","author":"Ghiani","year":"2010","journal-title":"Mol. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1083\/jcb.143.4.957","article-title":"Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes","volume":"143","author":"Prekeris","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrm2999","article-title":"TRAPP complexes in membrane traffic: Convergence through a common Rab","volume":"11","author":"Barrowman","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/tra.12615","article-title":"TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)-associated proteins","volume":"20","author":"Sacher","year":"2019","journal-title":"Traffic"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"281","DOI":"10.15252\/embj.201592695","article-title":"TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic","volume":"35","author":"Lamb","year":"2016","journal-title":"EMBO J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"144005","DOI":"10.1016\/j.gene.2019.144005","article-title":"Structure, regulation, and (patho-)physiological functions of the stress-induced protein kinase CK1 delta (CSNK1D)","volume":"715","author":"Xu","year":"2019","journal-title":"Gene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1016\/j.febslet.2014.09.032","article-title":"Hrr25 phosphorylates the autophagic receptor Atg34 to promote vacuolar transport of alpha-mannosidase under nitrogen starvation conditions","volume":"588","author":"Mochida","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1083\/jcb.201402128","article-title":"Hrr25 triggers selective autophagy-related pathways by phosphorylating receptor proteins","volume":"207","author":"Tanaka","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"862","DOI":"10.15252\/embr.201438932","article-title":"Hrr25 kinase promotes selective autophagy by phosphorylating the cargo receptor Atg19","volume":"15","author":"Pfaffenwimmer","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1083\/jcb.201408075","article-title":"Ypt1\/Rab1 regulates Hrr25\/CK1delta kinase activity in ER-Golgi traffic and macroautophagy","volume":"210","author":"Wang","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35036035","article-title":"The versatility and universality of calcium signalling","volume":"1","author":"Berridge","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-981-15-0602-4_7","article-title":"Ca(2+) Ion and Autophagy","volume":"1206","author":"Hu","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ceca.2011.04.001","article-title":"A dual role for Ca(2+) in autophagy regulation","volume":"50","author":"Decuypere","year":"2011","journal-title":"Cell Calcium"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/15548627.2017.1384887","article-title":"Ion channels in the regulation of autophagy","volume":"14","author":"Kondratskyi","year":"2018","journal-title":"Autophagy"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.molcel.2017.08.005","article-title":"The ER-Localized Transmembrane Protein EPG-3\/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation","volume":"67","author":"Zhao","year":"2017","journal-title":"Mol. 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