Volume 12 Issue 7
Jul.  2021
Turn off MathJax
Article Contents
Linsen Li, Mindan Tong, Yuhui Fu, Fang Chen, Shen Zhang, Hanmo Chen, Xi Ma, Defa Li, Xiaoxia Liu, Qing Zhong. Lipids and membrane-associated proteins in autophagy[J]. Protein&Cell, 2021, 12(7): 520-544. doi: 10.1007/s13238-020-00793-9
Citation: Linsen Li, Mindan Tong, Yuhui Fu, Fang Chen, Shen Zhang, Hanmo Chen, Xi Ma, Defa Li, Xiaoxia Liu, Qing Zhong. Lipids and membrane-associated proteins in autophagy[J]. Protein&Cell, 2021, 12(7): 520-544. doi: 10.1007/s13238-020-00793-9

Lipids and membrane-associated proteins in autophagy

doi: 10.1007/s13238-020-00793-9

The work was supported by grants from NSFC (91754205, 91957204, 31771523, 31870830 and 31801170), MOST (2019YFA0508602), Shanghai Municipal Science and Technology Project (20JC1411100), Program of Shanghai Academic/Technology Research Leader (19XD1402200) and innovative research team of high-level local universities in Shanghai.

  • Received Date: 2020-07-02
  • Rev Recd Date: 2020-08-07
  • Publish Date: 2021-07-08
  • Autophagy is essential for the maintenance of cellular homeostasis and its dysfunction has been linked to various diseases. Autophagy is a membrane driven process and tightly regulated by membrane-associated proteins. Here, we summarized membrane lipid composition, and membrane-associated proteins relevant to autophagy from a spatiotemporal perspective. In particular, we focused on three important membrane remodeling processes in autophagy, lipid transfer for phagophore elongation, membrane scission for phagophore closure, and autophagosome-lysosome membrane fusion. We discussed the significance of the discoveries in this field and possible avenues to follow for future studies. Finally, we summarized the membrane-associated biochemical techniques and assays used to study membrane properties, with a discussion of their applications in autophagy.
  • loading
  • [1]
    Abada A, Levin-Zaidman S, Porat Z, Dadosh T, Elazar Z (2017) SNARE priming is essential for maturation of autophagosomes but not for their formation. Proc Natl Acad Sci USA 114:12749-12754
    Asao H, Sasaki Y, Arita T, Tanaka N, Endo K, Kasai H, Takeshita T, Endo Y, Fujita T, Sugamura K (1997) Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth. J Biol Chem 272:32785-32791
    Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL, Habermann A, Griffiths G, Ktistakis NT (2008) Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 182:685-701
    Baba T, Toth DJ, Sengupta N, Kim YJ, Balla T (2019) Phosphatidylinositol 4,5-bisphosphate controls Rab7 and PLEKHM1 membrane cycling during autophagosome-lysosome fusion. EMBO J 38:e100312
    Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD (2002a) Escrt-Ⅲ:an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell 3:271-282
    Babst M, Katzmann DJ, Snyder WB, Wendland B, Emr SD (2002b) Endosome-associated complex, ESCRT-Ⅱ, recruits transport machinery for protein sorting at the multivesicular body. Dev Cell 3:283-289
    Baskaran S, Ragusa MJ, Boura E, Hurley JH (2012) Two-site recognition of phosphatidylinositol 3-phosphate by PROPPINs in autophagy. Mol Cell 47:339-348
    Bas L, Papinski D, Licheva M, Torggler R, Rohringer S, Schuschnig M, Kraft C (2018) Reconstitution reveals Ykt6 as the autophagosomal SNARE in autophagosome-vacuole fusion. J Cell Biol 217:3656-3669
    Bean BD, Dziurdzik SK, Kolehmainen KL, Fowler CM, Kwong WK, Grad LI, Davey M, Schluter C, Conibear E (2018) Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites. J Cell Biol 217:3593-3607
    Behrends C, Sowa ME, Gygi SP, Harper JW (2010) Network organization of the human autophagy system. Nature 466:68-76
    Besprozvannaya M, Dickson E, Li H, Ginburg KS, Bers DM, Auwerx J, Nunnari J (2018) GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells. Elife 7:e31019
    Bian X, Zhang Z, Xiong Q, De Camilli P, Lin C (2019) A programmable DNA-origami platform for studying lipid transfer between bilayers. Nat Chem Biol 15:830-837
    Bielli A, Haney CJ, Gabreski G, Watkins SC, Bannykh SI, Aridor M (2005) Regulation of Sar1 NH2 terminus by GTP binding and hydrolysis promotes membrane deformation to control COPⅡ vesicle fission. The Journal of cell biology 171:919-924
    Buchkovich NJ, Henne WM, Tang S, Emr SD (2013) Essential N-terminal insertion motif anchors the ESCRT-Ⅲ filament during MVB vesicle formation. Dev Cell 27:201-214
    Caillat C, Macheboeuf P, Wu Y, McCarthy AA, Boeri-Erba E, Effantin G, Gottlinger HG, Weissenhorn W, Renesto P (2015) Asymmetric ring structure of Vps4 required for ESCRT-Ⅲ disassembly. Nat Commun 6:8781
    Carlsson SR, Simonsen A (2015) Membrane dynamics in autophagosome biogenesis. J Cell Sci 128:193-205
    Carroll B, Mohd-Naim N, Maximiano F, Frasa MA, McCormack J, Finelli M, Thoresen SB, Perdios L, Daigaku R, Francis RE et al (2013) The TBC/RabGAP Armus coordinates Rac1 and Rab7 functions during autophagy. Dev Cell 25:15-28
    Chang C, Young LN, Morris KL, von Bülow S, Schöneberg J, Yamamoto-Imoto H, Oe Y, Yamamoto K, Nakamura S, Stjepanovic G (2019) Bidirectional control of autophagy by BECN1 BARA domain dynamics. Mol Cell 73(339-353):e336
    Chan EY, Longatti A, McKnight NC, Tooze SA (2009) Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol 29:157-171
    Chen D, Fan W, Lu Y, Ding X, Chen S, Zhong Q (2012) A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate. Mol Cell 45:629-641
    Chiaruttini N, Redondo-Morata L, Colom A, Humbert F, Lenz M, Scheuring S, Roux A (2015) Relaxation of loaded ESCRT-Ⅲ spiral springs drives membrane deformation. Cell 163:866-879
    Chowdhury S, Otomo C, Leitner A, Ohashi K, Aebersold R, Lander GC, Otomo T (2018) Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2A-WIPI4 complex. Proc Natl Acad Sci 115:E9792-E9801
    Chung T (2019) How phosphoinositides shape autophagy in plant cells. Plant Sci 281:146-158
    Cudjoe EK Jr, Saleh T, Hawkridge AM, Gewirtz DA (2017) Proteomics insights into autophagy. Proteomics 17:1700022
    Daum G, Vance JE (1997) Import of lipids into mitochondria. Prog Lipid Res 36:103-130
    de la Ballina LR, Munson MJ, Simonsen A (2020) Lipids and lipid-binding proteins in selective autophagy. J Mol Biol 432:135-159
    de Kroon AI, Dolis D, Mayer A, Lill R, de Kruijff B (1997) Phospholipid composition of highly purified mitochondrial outer membranes of rat liver and Neurospora crassa. Is cardiolipin present in the mitochondrial outer membrane? Biochim Biophys Acta (BBA) 1325:108-116
    Delorme-Axford E, Klionsky DJ (2018) Transcriptional and post-transcriptional regulation of autophagy in the yeast Saccharomyces cerevisiae. J Biol Chem 293:5396-5403
    Diao J, Ishitsuka Y, Lee H, Joo C, Su Z, Syed S, Shin YK, Yoon TY, Ha T (2012) A single vesicle-vesicle fusion assay for in vitro studies of SNAREs and accessory proteins. Nat Protoc 7:921-934
    Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y, Zhou Q, Wilz LM, Li J, Vivona S et al (2015) ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature 520:563-566
    Dikic I, Elazar Z (2018) Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol 19:349-364
    Ding X, Jiang X, Tian R, Zhao P, Li L, Wang X, Chen S, Zhu Y, Mei M, Bao S et al (2019) RAB2 regulates the formation of autophagosome and autolysosome in mammalian cells. Autophagy 15:1774-1786
    Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651-657
    Dove SK, Dong K, Kobayashi T, Williams FK, Michell RH (2009) Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function. Biochem J 419:1-13
    Dudley LJ, Cabodevilla AG, Makar AN, Sztacho M, Michelberger T, Marsh JA, Houston DR, Martens S, Jiang X, Gammoh N (2019) Intrinsic lipid binding activity of ATG16L1 supports efficient membrane anchoring and autophagy. EMBO J 38:e100554
    Ebner P, Poetsch I, Deszcz L, Hoffmann T, Zuber J, Ikeda F (2018) The IAP family member BRUCE regulates autophagosome-lysosome fusion. Nat Commun 9:1-15
    Fan W, Nassiri A, Zhong Q (2011) Autophagosome targeting and membrane curvature sensing by Barkor/Atg14 (L). Proc Natl Acad Sci USA 108:7769-7774
    Feng Q, Luo Y, Zhang XN, Yang XF, Hong XY, Sun DS, Li XC, Hu Y, Li XG, Zhang JF et al (2020) MAPT/Tau accumulation represses autophagy flux by disrupting IST1-regulated ESCRT-Ⅲ complex formation:a vicious cycle in Alzheimer neurodegeneration. Autophagy 16:641-658
    Fujioka Y, Noda NN, Nakatogawa H, Ohsumi Y, Inagaki F (2010) Dimeric coiled-coil structure of Saccharomyces cerevisiae Atg16 and its functional significance in autophagy. J Biol Chem 285:1508-1515
    Fujioka Y, Alam JM, Noshiro D, Mouri K, Ando T, Okada Y, May AI, Knorr RL, Suzuki K, Ohsumi Y et al (2020) Phase separation organizes the site of autophagosome formation. Nature 578:301-305
    Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T (2008) The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell 19:2092-2100
    Gatica D, Lahiri V, Klionsky DJ (2018) Cargo recognition and degradation by selective autophagy. Nat Cell Biol 20:233-242
    Gatta AT, Carlton JG (2019) The ESCRT-machinery:closing holes and expanding roles. Curr Opin Cell Biol 59:121-132
    Ge L, Schekman R (2014) The ER-Golgi intermediate compartment feeds the phagophore membrane. Autophagy 10:170-172
    Ge L, Melville D, Zhang M, Schekman R (2013) The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis. Elife 2:e00947
    Ge L, Zhang M, Schekman R (2014) Phosphatidylinositol 3-kinase and COPⅡ generate LC3 lipidation vesicles from the ER-Golgi intermediate compartment. elife 3:e04135
    Ge L, Zhang M, Kenny SJ, Liu D, Maeda M, Saito K, Mathur A, Xu K, Schekman R (2017) Remodeling of ER-exit sites initiates a membrane supply pathway for autophagosome biogenesis. EMBO Rep 18:1586-1603
    Gómez-Sánchez R, Rose J, Guimarães R, Mari M, Papinski D, Rieter E, Geerts WJ, Hardenberg R, Kraft C, Ungermann C (2018) Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores. J Cell Biol 217:2743-2763
    Graef M (2020) Recent advances in the understanding of autophagosome biogenesis. F1000Res 9.
    Graef M, Friedman JR, Graham C, Babu M, Nunnari J (2013) ER exit sites are physical and functional core autophagosome biogenesis components. Mol Biol Cell 24:2918-2931
    Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R, Kim PK, Lippincott-Schwartz J (2010) Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141:656-667
    Hanada T, Noda NN, Satomi Y, Ichimura Y, Fujioka Y, Takao T, Inagaki F, Ohsumi Y (2007) The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem 282:37298-37302
    Hasegawa J, Iwamoto R, Otomo T, Nezu A, Hamasaki M, Yoshimori T (2016) Autophagosome-lysosome fusion in neurons requires INPP5E, a protein associated with Joubert syndrome. EMBO J 35:1853-1867
    Hayashi-Nishino M, Fujita N, Noda T, Yamaguchi A, Yoshimori T, Yamamoto A (2009) A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol 11:1433-1437
    He S, Ni D, Ma B, Lee J-H, Zhang T, Ghozalli I, Pirooz SD, Zhao Z, Bharatham N, Li B (2013) PtdIns (3) P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex. Nat Cell Biol 15:1206-1219
    Hollenstein DM, Kraft C (2020) Autophagosomes are formed at a distinct cellular structure. Curr Opin Cell Biol 65:50-57
    Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N et al (2009) Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 20:1981-1991
    Ho CY, Alghamdi TA, Botelho RJ (2012) Phosphatidylinositol-3,5-bisphosphate:no longer the poor PIP2. Traffic 13:1-8
    Huang X, Sun S, Wang X, Fan F, Zhou Q, Lu S, Cao Y, Wang QW, Dong MQ, Yao J et al (2019) Mechanistic insights into the SNARE complex disassembly. Sci Adv 5:eaau8164
    Hurley JH, Young LN (2017) Mechanisms of autophagy initiation. Annu Rev Biochem 86:225-244
    Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M et al (2000) A ubiquitin-like system mediates protein lipidation. Nature 408:488-492
    Ishihara N, Hamasaki M, Yokota S, Suzuki K, Kamada Y, Kihara A, Yoshimori T, Noda T, Ohsumi Y (2001) Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol Biol Cell 12:3690-3702
    Itakura E, Kishi-Itakura C, Mizushima N (2012) The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell 151:1256-1269
    Jang DJ, Lee JA (2016) The roles of phosphoinositides in mammalian autophagy. Arch Pharm Res 39:1129-1136
    Jeynov B, Lay D, Schmidt F, Tahirovic S, Just WW (2006) Phosphoinositide synthesis and degradation in isolated rat liver peroxisomes. FEBS Lett 580:5917-5924
    Jiang P, Nishimura T, Sakamaki Y, Itakura E, Hatta T, Natsume T, Mizushima N (2014) The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17. Mol Biol Cell 25:1327-1337
    Johansen T, Lamark T (2020) Selective autophagy:ATG8 family proteins, LIR motifs and cargo receptors. J Mol Biol 432:80-103
    Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH (2009) ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 20:1992-2003
    Jun Y, Wickner W (2007) Assays of vacuole fusion resolve the stages of docking, lipid mixing, and content mixing. Proc Natl Acad Sci 104:13010-13015
    Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720-5728
    Karanasios E, Stapleton E, Manifava M, Kaizuka T, Mizushima N, Walker SA, Ktistakis NT (2013) Dynamic association of the ULK1 complex with omegasomes during autophagy induction. J Cell Sci 126:5224-5238
    Katzmann DJ, Babst M, Emr SD (2001) Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106:145-155
    Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T, Noda T, Ohsumi Y (1999) Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol 147:435-446
    Knaevelsrud H, Soreng K, Raiborg C, Haberg K, Rasmuson F, Brech A, Liestol K, Rusten TE, Stenmark H, Neufeld TP et al (2013) Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation. J Cell Biol 202:331-349
    Komada M, Kitamura N (1995) Growth factor-induced tyrosine phosphorylation of Hrs, a novel 115-kilodalton protein with a structurally conserved putative zinc finger domain. Mol Cell Biol 15:6213-6221
    Kostelansky MS, Schluter C, Tam YY, Lee S, Ghirlando R, Beach B, Conibear E, Hurley JH (2007) Molecular architecture and functional model of the complete yeast ESCRT-I heterotetramer. Cell 129:485-498
    Kriegenburg F, Ungermann C, Reggiori F (2018) Coordination of autophagosome-lysosome fusion by ATG8 family members. Curr Biol 28:R512-R518
    Kriegenburg F, Bas L, Gao J, Ungermann C, Kraft C (2019) The multi-functional SNARE protein Ykt6 in autophagosomal fusion processes. Cell Cycle 18:639-651
    Ktistakis NT (2019) Who plays the ferryman:ATG2 channels lipids into the forming autophagosome. J Cell Biol 218:1767
    Kumar N, Leonzino M, Hancock-Cerutti W, Horenkamp FA, Li P, Lees JA, Wheeler H, Reinisch KM, De Camilli P (2018) VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites. J Cell Biol 217:3625-3639
    Kyoung M, Srivastava A, Zhang Y, Diao J, Vrljic M, Grob P, Nogales E, Chu S, Brunger AT (2011) In vitro system capable of differentiating fast Ca2+-triggered content mixing from lipid exchange for mechanistic studies of neurotransmitter release. Proc Natl Acad Sci 108:E304-E313
    Kyoung M, Zhang Y, Diao J, Chu S, Brunger AT (2013) Studying calcium-triggered vesicle fusion in a single vesicle-vesicle content and lipid-mixing system. Nat Protoc 8:1-16
    Lai LTF, Ye H, Zhang W, Jiang L, Lau WCY (2019) Structural biology and electron microscopy of the autophagy molecular machinery. Cells 8:1627
    Laraia L, Friese A, Corkery DP, Konstantinidis G, Erwin N, Hofer W, Karatas H, Klewer L, Brockmeyer A, Metz M (2019) The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis. Nat Chem Biol 15:710-720
    Lemus L, Ribas JL, Sikorska N, Goder V (2016) An ER-localized SNARE protein is exported in specific COPⅡ vesicles for autophagosome biogenesis. Cell Rep 14:1710-1722
    Levine B, Kroemer G (2019) Biological functions of autophagy genes:a disease perspective. Cell 176:11-42
    Liang C, Lee JS, Inn KS, Gack MU, Li Q, Roberts EA, Vergne I, Deretic V, Feng P, Akazawa C et al (2008) Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol 10:776-787
    Liu X, Seven AB, Camacho M, Esser V, Xu J, Trimbuch T, Quade B, Su L, Ma C, Rosenmund C et al (2016) Functional synergy between the Munc13 C-terminal C1 and C2 domains. Elife 5:e13696
    Liu X, Seven AB, Xu J, Esser V, Su L, Ma C, Rizo J (2017) Simultaneous lipid and content mixing assays for in vitro reconstitution studies of synaptic vesicle fusion. Nat Protoc 12:2014-2028
    Li L, Zhong Q (2016) Autophagosome-lysosome fusion:PIs to the rescue. EMBO J 35:1845-1847
    Lystad AH, Simonsen A (2016) Phosphoinositide-binding proteins in autophagy. FEBS Lett 590:2454-2468
    Lystad AH, Carlsson SR, Laura R, Kauffman KJ, Nag S, Yoshimori T, Melia TJ, Simonsen A (2019) Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes. Nat Cell Biol 21:372-383
    Maeda S, Otomo C, Otomo T (2019) The autophagic membrane tether ATG2A transfers lipids between membranes. Elife 8:e45777
    Maruyama T, Noda NN (2018) Autophagy-regulating protease Atg4:structure, function, regulation and inhibition. J Antibiot 71:72-78
    Matsui T, Jiang P, Nakano S, Sakamaki Y, Yamamoto H, Mizushima N (2018) Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17. J Cell Biol 217:2633-2645
    Matsushita M, Suzuki NN, Obara K, Fujioka Y, Ohsumi Y, Inagaki F (2007) Structure of Atg5.Atg16, a complex essential for autophagy. J Biol Chem 282:6763-6772
    Ma C, Su L, Seven AB, Xu Y, Rizo J (2013) Reconstitution of the vital functions of Munc18 and Munc13 in neurotransmitter release. Science 339:421-425
    Ma M, Liu J-J, Li Y, Huang Y, Ta N, Chen Y, Fu H, Ye M-D, Ding Y, Huang W (2017) Cryo-EM structure and biochemical analysis reveal the basis of the functional difference between human PI3KC3-C1 and-C2. Cell Res 27:989-1001
    McEwan DG, Popovic D, Gubas A, Terawaki S, Suzuki H, Stadel D, Coxon FP, Miranda de Stegmann D, Bhogaraju S, Maddi K et al (2015) PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins. Mol Cell 57:39-54
    Melia TJ, Lystad AH, Simonsen A (2020) Autophagosome biogenesis:from membrane growth to closure. J Cell Biol 219:e202002085
    Mercer TJ, Gubas A, Tooze SA (2018) A molecular perspective of mammalian autophagosome biogenesis. J Biol Chem 293:5386-5395
    Miao G, Zhang Y, Chen D, Zhang H (2020) The ER-localized transmembrane protein TMEM39A/SUSR2 regulates autophagy by controlling the trafficking of the PtdIns(4)P phosphatase SAC1. Mol Cell 77(618-632):e615
    Mizushima N (2007) Autophagy:process and function. Genes Dev 21:2861-2873
    Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107-132
    Moreau K, Ravikumar B, Renna M, Puri C, Rubinsztein DC (2011) Autophagosome precursor maturation requires homotypic fusion. Cell 146:303-317
    Muñoz-Braceras S, Calvo R, Escalante R (2015) TipC and the chorea-acanthocytosis protein VPS13A regulate autophagy in Dictyostelium and human HeLa cells. Autophagy 11:918-927
    Nair U, Jotwani A, Geng J, Gammoh N, Richerson D, Yen W-L, Griffith J, Nag S, Wang K, Moss T (2011) SNARE proteins are required for macroautophagy. Cell 146:290-302
    Naito T, Ercan B, Krshnan L, Triebl A, Koh DHZ, Wei F-Y, Tomizawa K, Torta FT, Wenk MR, Saheki Y (2019) Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex. eLife 8:e51401
    Nakamura S, Yoshimori T (2017) New insights into autophagosome-lysosome fusion. J Cell Sci 130:1209-1216
    Nakatogawa H (2020) Mechanisms governing autophagosome biogenesis. Nat Rev Mol Cell Biol
    Nakatogawa H, Ichimura Y, Ohsumi Y (2007) Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 130:165-178
    Nascimbeni AC, Codogno P, Morel E (2017) Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics. FEBS J 284:1267-1278
    Nath S, Dancourt J, Shteyn V, Puente G, Fong WM, Nag S, Bewersdorf J, Yamamoto A, Antonny B, Melia TJ (2014) Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3. Nat Cell Biol 16:415-424
    Nishimura T, Tooze SA (2020) Emerging roles of ATG proteins and membrane lipids in autophagosome formation. Cell Discov 6:32
    Odorizzi G, Babst M, Emr SD (1998) Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell 95:847-858
    Ogawa M, Yoshikawa Y, Kobayashi T, Mimuro H, Fukumatsu M, Kiga K, Piao Z, Ashida H, Yoshida M, Kakuta S (2011) A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens. Cell Host Microbe 9:376-389
    Omari S, Makareeva E, Roberts-Pilgrim A, Mirigian L, Jarnik M, Ott C, Lippincott-Schwartz J, Leikin S (2018) Noncanonical autophagy at ER exit sites regulates procollagen turnover. Proc Natl Acad Sci 115:E10099-E10108
    Osawa T, Noda NN (2019) Atg2:A novel phospholipid transfer protein that mediates de novo autophagosome biogenesis. Protein Sci 28:1005-1012
    Osawa T, Alam JM, Noda NN (2019a) Membrane-binding domains in autophagy. Chem Phys Lipids 218:1-9
    Osawa T, Ishii Y, Noda NN (2019b) Human ATG2B possesses a lipid transfer activity which is accelerated by negatively charged lipids and WIPI4. Genes Cells 25:65
    Osawa T, Kotani T, Kawaoka T, Hirata E, Suzuki K, Nakatogawa H, Ohsumi Y, Noda NN (2019c) Atg2 mediates direct lipid transfer between membranes for autophagosome formation. Nat Struct Mol Biol 26:281-288
    Otomo T, Maeda S (2019) ATG2A transfers lipids between membranes in vitro. Autophagy 15:2031-2032
    Otomo T, Chowdhury S, Lander GC (2018) The rod-shaped ATG2A-WIPI4 complex tethers membranes in vitro. Contact 1:2515256418819936
    Palamiuc L, Ravi A, Emerling BM (2020) Phosphoinositides in autophagy:current roles and future insights. FEBS J 287:222-238
    Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282:24131-24145
    Petiot A, Ogier-Denis E, Blommaart EF, Meijer AJ, Codogno P (2000) Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem 275:992-998
    Polson HE, de Lartigue J, Rigden DJ, Reedijk M, Urbé S, Clague MJ, Tooze SA (2010) Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy 6:506-522
    Preiss R (2017) Autophagy gene overexpression in Saccharomyces cerevisiae for accelerated sparkling wine production
    Puri C, Renna M, Bento CF, Moreau K, Rubinsztein DC (2013) Diverse autophagosome membrane sources coalesce in recycling endosomes. Cell 154:1285-1299
    Ragusa MJ, Stanley RE, Hurley JH (2012) Architecture of the Atg17 complex as a scaffold for autophagosome biogenesis. Cell 151:1501-1512
    Ravikumar B, Moreau K, Jahreiss L, Puri C, Rubinsztein DC (2010) Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat Cell Biol 12:747-757
    Raymond CK, Howald-Stevenson I, Vater CA, Stevens TH (1992) Morphological classification of the yeast vacuolar protein sorting mutants:evidence for a prevacuolar compartment in class E vps mutants. Mol Biol Cell 3:1389-1402
    Reggiori F, Ungermann C (2017) Autophagosome maturation and fusion. J Mol Biol 429:486-496
    Reggiori F, Shintani T, Chong H, Nair U, Klionsky DJ (2005) Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts. Autophagy 1:101-109
    Romanov J, Walczak M, Ibiricu I, Schuchner S, Ogris E, Kraft C, Martens S (2012) Mechanism and functions of membrane binding by the Atg5-Atg12/Atg16 complex during autophagosome formation. EMBO J 31:4304-4317
    Rong Y, Liu M, Ma L, Du W, Zhang H, Tian Y, Cao Z, Li Y, Ren H, Zhang C et al (2012) Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. Nat Cell Biol 14:924-934
    Russell RC, Tian Y, Yuan H, Park HW, Chang YY, Kim J, Kim H, Neufeld TP, Dillin A, Guan KL (2013) ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol 15:741-750
    Rusten TE, Stenmark H (2009) How do ESCRT proteins control autophagy? J Cell Sci 122:2179-2183
    Schoneberg J, Lee IH, Iwasa JH, Hurley JH (2017) Reverse-topology membrane scission by the ESCRT proteins. Nat Rev Mol Cell Biol 18:5-17
    Schoneberg J, Pavlin MR, Yan S, Righini M, Lee IH, Carlson LA, Bahrami AH, Goldman DH, Ren X, Hummer G et al (2018) ATP-dependent force generation and membrane scission by ESCRT-Ⅲ and Vps4. Science 362:1423-1428
    Schütter M, Giavalisco P, Brodesser S, Graef M (2020) Local fatty acid channeling into phospholipid synthesis drives phagophore expansion during autophagy. Cell 180(135-149):e114
    Schu PV, Takegawa K, Fry MJ, Stack JH, Waterfield MD, Emr SD (1993) Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science 260:88-91
    Shatz O, Holland P, Elazar Z, Simonsen A (2016) Complex relations between phospholipids, autophagy, and neutral lipids. Trends Biochem Sci 41:907-923
    Shibutani ST, Yoshimori T (2014) A current perspective of autophagosome biogenesis. Cell Res 24:58-68
    Shima T, Kirisako H, Nakatogawa H (2019) COPⅡ vesicles contribute to autophagosomal membranes. J Cell Biol 218:1503-1510
    Shintani T, Suzuki K, Kamada Y, Noda T, Ohsumi Y (2001) Apg2p functions in autophagosome formation on the perivacuolar structure. J Biol Chem 276:30452-30460
    Sitarska E, Xu J, Park S, Liu X, Quade B, Stepien K, Sugita K, Brautigam CA, Sugita S, Rizo J (2017) Autoinhibition of Munc18-1 modulates synaptobrevin binding and helps to enable Munc13-dependent regulation of membrane fusion. Elife 6:e24278
    Slessareva JE, Routt SM, Temple B, Bankaitis VA, Dohlman HG (2006) Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein α subunit at the endosome. Cell 126:191-203
    Soreng K, Munson MJ, Lamb CA, Bjorndal GT, Pankiv S, Carlsson SR, Tooze SA, Simonsen A (2018) SNX18 regulates ATG9A trafficking from recycling endosomes by recruiting Dynamin-2. EMBO Rep 19:e44837
    Stadel D, Millarte V, Tillmann KD, Huber J, Tamin-Yecheskel BC, Akutsu M, Demishtein A, Ben-Zeev B, Anikster Y, Perez F et al (2015) TECPR2 cooperates with LC3C to regulate COPⅡ-dependent ER export. Mol cell 60:89-104
    Stroupe C, Collins KM, Fratti RA, Wickner W (2006) Purification of active HOPS complex reveals its affinities for phosphoinositides and the SNARE Vam7p. EMBO J 25:1579-1589
    Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q (2008) Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class Ⅲ phosphatidylinositol 3-kinase. Proc Natl Acad Sci 105:19211-19216
    Sun Q, Zhang J, Fan W, Wong KN, Ding X, Chen S, Zhong Q (2011) The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression. J Biol Chem 286:185-191
    Suzuki H, Osawa T, Fujioka Y, Noda NN (2017) Structural biology of the core autophagy machinery. Curr Opin Struct Biol 43:10-17
    Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sun M, Sato Y, Liang C, Jung JU, Cheng JQ, Mul JJ (2007) Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol 9:1142-1151
    Takahashi Y, Meyerkord CL, Hori T, Runkle K, Fox TE, Kester M, Loughran TP, Wang HG (2011) Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy. Autophagy 7:61-73
    Takahashi Y, He H, Tang Z, Hattori T, Liu Y, Young MM, Serfass JM, Chen L, Gebru M, Chen C et al (2018) An autophagy assay reveals the ESCRT-Ⅲ component CHMP2A as a regulator of phagophore closure. Nat Commun 9:2855
    Takahashi Y, Liang X, Hattori T, Tang Z, He H, Chen H, Liu X, Abraham T, Imamura-Kawasawa Y, Buchkovich NJ et al (2019) VPS37A directs ESCRT recruitment for phagophore closure. J Cell Biol 218:3336-3354
    Takamori S, Holt M, Stenius K, Lemke EA, Gronborg M, Riedel D, Urlaub H, Schenck S, Brugger B, Ringler P et al (2006) Molecular anatomy of a trafficking organelle. Cell 127:831-846
    Tang Z, Takahashi Y, He H, Hattori T, Chen C, Liang X, Chen H, Young MM, Wang HG (2019) TOM40 targets Atg2 to mitochondria-associated ER membranes for phagophore expansion. Cell Rep 28(1744-1757):e1745
    Thorburn A (2018) Autophagy and disease. J Biol Chem 293:5425-5430
    Tong J, Manik MK, Im YJ (2018) Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites. Proc Natl Acad Sci 115:E856-E865
    Tsuboyama K, Koyama-Honda I, Sakamaki Y, Koike M, Morishita H, Mizushima N (2016) The ATG conjugation systems are important for degradation of the inner autophagosomal membrane. Science 354:1036-1041
    Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169-174
    Valverde DP, Yu S, Boggavarapu V, Kumar N, Lees JA, Walz T, Reinisch KM, Melia TJ (2019) ATG2 transports lipids to promote autophagosome biogenesis. J Cell Biol 218:1787-1798
    Velikkakath AK, Nishimura T, Oita E, Ishihara N, Mizushima N (2012) Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets. Mol Biol Cell 23:896-909
    Wang K, Yang Z, Liu X, Mao K, Nair U, Klionsky DJ (2012) Phosphatidylinositol 4-kinases are required for autophagic membrane trafficking. J Biol Chem 287:37964-37972
    Wang Z, Miao G, Xue X, Guo X, Yuan C, Wang Z, Zhang G, Chen Y, Feng D, Hu J (2016) The Vici syndrome protein EPG5 is a Rab7 effector that determines the fusion specificity of autophagosomes with late endosomes/lysosomes. Mol Cell 63:781-795
    Watanabe Y, Kobayashi T, Yamamoto H, Hoshida H, Akada R, Inagaki F, Ohsumi Y, Noda NN (2012) Structure-based analyses reveal distinct binding sites for Atg2 and phosphoinositides in Atg18. J Biol Chem 287:31681-31690
    Weber T, Zemelman BV, McNew JA, Westermann B, Gmachl M, Parlati F, Söllner TH, Rothman JE (1998) SNAREpins:minimal machinery for membrane fusion. Cell 92:759-772
    Wetzel L, Blanchard S, Rama S, Beier V, Kaufmann A, Wollert T (2020) TECPR1 promotes aggrephagy by direct recruitment of LC3C autophagosomes to lysosomes. Nat Commun 11:1-16
    Wherrett JR, Huterer S (1972) Enrichment of bis-(monoacylglyceryl) phosphate in lysosomes from rat liver. J Biol Chem 247:4114-4120
    White KI, Zhao M, Choi UB, Pfuetzner RA, Brunger AT (2018) Structural principles of SNARE complex recognition by the AAA+ protein NSF. Elife 7:e38888
    Wickner W, Rizo J (2017) A cascade of multiple proteins and lipids catalyzes membrane fusion. Mol Biol Cell 28:707-711
    Wollert T, Hurley JH (2010) Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature 464:864-869
    Xie Z, Nair U, Klionsky DJ (2008) Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell 19:3290-3298
    Xu Z, Yang L, Xu S, Zhang Z, Cao Y (2015) The receptor proteins:pivotal roles in selective autophagy. Acta Biochim Biophys Sin 47:571-580
    Xu J, Camacho M, Xu Y, Esser V, Liu X, Trimbuch T, Pan YZ, Ma C, Tomchick DR, Rosenmund C et al (2017) Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN. Elife 6:e22567
    Yamamoto H, Kakuta S, Watanabe TM, Kitamura A, Sekito T, Kondo-Kakuta C, Ichikawa R, Kinjo M, Ohsumi Y (2012) Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol 198:219-233
    Ylä-Anttila P, Vihinen H, Jokitalo E, Eskelinen E-L (2009) 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy 5:1180-1185
    Yorikawa C, Shibata H, Waguri S, Hatta K, Horii M, Katoh K, Kobayashi T, Uchiyama Y, Maki M (2005) Human CHMP6, a myristoylated ESCRT-Ⅲ protein, interacts directly with an ESCRT-Ⅱ component EAP20 and regulates endosomal cargo sorting. Biochem J 387:17-26
    Yu Z-Q, Ni T, Hong B, Wang H-Y, Jiang F-J, Zou S, Chen Y, Zheng X-L, Klionsky DJ, Liang Y (2012) Dual roles of Atg8- PE deconjugation by Atg4 in autophagy. Autophagy 8:883-892
    Yu H, Rathore SS, Lopez JA, Davis EM, James DE, Martin JL, Shen J (2013) Comparative studies of Munc18c and Munc18-1 reveal conserved and divergent mechanisms of Sec1/Munc18 proteins. Proc Natl Acad Sci USA 110:E3271-3280
    Yu L, Chen Y, Tooze SA (2018) Autophagy pathway:cellular and molecular mechanisms. Autophagy 14:207-215
    Zambrano F, Fleischer S, Fleischer B (1975) Lipid composition of the Golgi apparatus of rat kidney and liver in comparison with other subcellular organelles. Biochim Biophys Acta (BBA) 380:357-369
    Zhang X, Wang L, Ireland SC, Ahat E, Li J, Bekier ME, Zhang Z, Wang Y (2019) GORASP2/GRASP55 collaborates with the PtdIns3K UVRAG complex to facilitate autophagosome-lysosome fusion. Autophagy 15:1787-1800
    Zhang A, Meng Y, Li Q, Liang Y (2020) The ESCRT complex negatively regulates Erg6 degradation under specific glucose restriction conditions. Traffic
    Zhao YG, Zhang H (2019) Autophagosome maturation:an epic journey from the ER to lysosomes. J Cell Biol 218:757-770
    Zhao M, Wu S, Zhou Q, Vivona S, Cipriano DJ, Cheng Y, Brunger AT (2015) Mechanistic insights into the recycling machine of the SNARE complex. Nature 518:61-67
    Zhen Y, Spangenberg H, Munson MJ, Brech A, Schink KO, Tan KW, Sorensen V, Wenzel EM, Radulovic M, Engedal N et al (2019) ESCRT-mediated phagophore sealing during mitophagy. Autophagy 2:1-16
    Zhou F, Wu Z, Zhao M, Murtazina R, Cai J, Zhang A, Li R, Sun D, Li W, Zhao L et al (2019) Rab5-dependent autophagosome closure by ESCRT. J Cell Biol 218:1908-1927
    Zinser E, Daum G (1995) Isolation and biochemical characterization of organelles from the yeast, Saccharomyces cerevisiae. Yeast 11:493-536
    Zucchi PC, Zick M (2011) Membrane fusion catalyzed by a Rab, SNAREs, and SNARE chaperones is accompanied by enhanced permeability to small molecules and by lysis. Mol Biol Cell 22:4635-4646
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索


    Article Metrics

    Article views (821) PDF downloads(112) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint