Molecular structures and function of the autophagosome-lysosome fusion machinery

References

• Zhao YG, Codogno P, Zhang H. Machinery, regulation and pathophysiological implications of autophagosome maturation. Nat Rev Mol Cell Biol. 2021;22:733–20.
   PubMed Web of Science ®Google Scholar
• Zhao YG, Zhang H. Autophagosome maturation: an epic journey from the ER to lysosomes. J Cell Biol. 2019;218:757–770.
   PubMed Web of Science ®Google Scholar
• Corona AK, Jackson WT. Finding the middle ground for autophagic fusion requirements. Trends Cell Biol. 2018;28:869–881.
   PubMed Web of Science ®Google Scholar
• Lőrincz P, Juhász G. Autophagosome-lysosome fusion. J Mol Biol. 2020;432:2462–2482.
   PubMed Web of Science ®Google Scholar
• Nakamura S, Yoshimori T. New insights into autophagosome-lysosome fusion. J Cell Sci. 2017;130:1209–1216.
   PubMed Web of Science ®Google Scholar
• Tian X, Teng J, Chen J. New insights regarding SNARE proteins in autophagosome-lysosome fusion. Autophagy. 2021;17:2680–2688.
   PubMed Web of Science ®Google Scholar
• Südhof TC, Rothman JE. Membrane fusion: grappling with SNARE and SM proteins. Science. 2009;323:474–477.
   PubMed Web of Science ®Google Scholar
• Söllner T, Whiteheart SW, Brunner M, et al. SNAP receptors implicated in vesicle targeting and fusion. Nature. 1993;362:318–324.
   PubMed Web of Science ®Google Scholar
• Fasshauer D, Sutton RB, Brunger AT, et al. Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs. Proc Natl Acad Sci U S A. 1998;95:15781–15786.
   PubMed Web of Science ®Google Scholar
• Lamb CA, Yoshimori T, Tooze SA. The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 2013;14:759–774.
   PubMed Web of Science ®Google Scholar
• Kloepper TH, Kienle CN, Fasshauer D. An elaborate classification of SNARE proteins sheds light on the conservation of the eukaryotic endomembrane system. Mol Biol Cell. 2007;18:3463–3471.
   PubMed Web of Science ®Google Scholar
• Sutton RB, Fasshauer D, Jahn R, et al. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature. 1998;395:347–353.
   PubMed Web of Science ®Google Scholar
• Tian Z, Gong J, Crowe M, et al. Biochemical studies of membrane fusion at the single-particle level. Prog Lipid Res. 2019;73:92–100.
   PubMed Web of Science ®Google Scholar
• Brunger AT, Cipriano DJ, Diao J. Towards reconstitution of membrane fusion mediated by SNAREs and other synaptic proteins. Crit Rev Biochem Mol Biol. 2015;50:231–241.
   PubMed Web of Science ®Google Scholar
• Jahn R, Scheller RH. SNAREs–engines for membrane fusion. Nat Rev Mol Cell Biol. 2006;7:631–643.
   PubMed Web of Science ®Google Scholar
• Furuta N, Fujita N, Noda T, et al. Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol Biol Cell. 2010;21:1001–1010.
   PubMed Web of Science ®Google Scholar
• Fader CM, Sánchez DG, Mestre MB, et al. TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta. 2009;1793:1901–1916.
   PubMed Web of Science ®Google Scholar
• Itakura E, Kishi-Itakura C, Mizushima N. The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell. 2012;151:1256–1269.
   PubMed Web of Science ®Google Scholar
• Takáts S, Nagy P, Varga Á, et al. Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila. J Cell Biol. 2013;201(4):531–539.
   PubMed Web of Science ®Google Scholar
• Diao J, Liu R, Rong Y, et al. ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature. 2015;520:563–566.
   PubMed Web of Science ®Google Scholar
• Bu B, Tian Z, Li D, et al. Double-transmembrane domain of SNAREs decelerates the fusion by increasing the protein-lipid mismatch. J Mol Biol. 2023;435:168089.
   PubMed Web of Science ®Google Scholar
• Matsui T, Jiang P, Nakano S, et al. Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17. J Cell Biol. 2018;217:2633–2645.
   PubMed Web of Science ®Google Scholar
• Bas L, Papinski D, Licheva M, et al. Reconstitution reveals Ykt6 as the autophagosomal SNARE in autophagosome-vacuole fusion. J Cell Biol. 2018;217:3656–3669.
   PubMed Web of Science ®Google Scholar
• Takáts S, Glatz G, Szenci G, et al. Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion. PLoS Genet. 2018;14:e1007359.
   PubMed Web of Science ®Google Scholar
• Malmersjö S, Di Palma S, Diao J, et al. Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion. EMBO J. 2016;35:1810–1821.
   PubMed Web of Science ®Google Scholar
• Wang L, Diao J. VAMP8 phosphorylation regulates lysosome dynamics during autophagy. Autophagy Rep. 2022;1:79–82.
   PubMedGoogle Scholar
• Guo B, Liang Q, Li L, et al. O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nat Cell Biol. 2014;16:1215–1226.
   PubMed Web of Science ®Google Scholar
• Wang P, Lazarus BD, Forsythe ME, et al. O-GlcNAc cycling mutants modulate proteotoxicity in Caenorhabditis elegans models of human neurodegenerative diseases. Proc Natl Acad Sci U S A. 2012;109:17669–17674.
   PubMed Web of Science ®Google Scholar
• Pellegrini FR, De Martino S, Fianco G, et al. Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production. Autophagy. 2023;19:2078–2093.
   PubMed Web of Science ®Google Scholar
• Chen Q, Hao M, Wang L, et al. Prefused lysosomes cluster on autophagosomes regulated by VAMP8. Cell Death Dis. 2021;12:939.
   PubMed Web of Science ®Google Scholar
• Huang H, Ouyang Q, Zhu M, et al. mTOR-mediated phosphorylation of VAMP8 and SCFD1 regulates autophagosome maturation. Nat Commun. 2021;12:6622.
   PubMed Web of Science ®Google Scholar
• Shen Q, Shi Y, Liu J, et al. Acetylation of STX17 (syntaxin 17) controls autophagosome maturation. Autophagy. 2021;17:1157–1169.
   PubMed Web of Science ®Google Scholar
• Kumar S, Gu Y, Abudu YP, et al. Phosphorylation of syntaxin 17 by TBK1 controls autophagy initiation. Dev Cell. 2019;49:130–144.e6.
   PubMed Web of Science ®Google Scholar
• Gao J, Kurre R, Rose J, et al. Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex. EMBO Rep. 2020;21:e50733.
   PubMed Web of Science ®Google Scholar
• Barz S, Kriegenburg F, Henning A, et al. Atg1 kinase regulates autophagosome-vacuole fusion by controlling SNARE bundling. EMBO Rep. 2020;21:e51869.
   PubMed Web of Science ®Google Scholar
• Sánchez-Martín P, Kriegenburg F, Alves L, et al. ULK1-mediated phosphorylation regulates the conserved role of YKT6 in autophagy. J Cell Sci. 2023;136:jcs260546.
   PubMed Web of Science ®Google Scholar
• Herrmann JM, Spang A. Intracellular parcel service: current issues in intracellular membrane trafficking. Methods Mol Biol. 2015;1270:1–12.
   PubMedGoogle Scholar
• Yu I-M, Hughson FM. Tethering factors as organizers of intracellular vesicular traffic. Annu Rev Cell Dev Biol. 2010;26:137–156.
   PubMed Web of Science ®Google Scholar
• Stanton AE, Hughson FM. The machinery of vesicle fusion. Curr Opin Cell Biol. 2023;83:102191.
   PubMed Web of Science ®Google Scholar
• Nickerson DP, Brett CL, Merz AJ. Vps-C complexes: gatekeepers of endolysosomal traffic. Curr Opin Cell Biol. 2009;21:543–551.
   PubMed Web of Science ®Google Scholar
• Takáts S, Pircs K, Nagy P, et al. Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila. Mol Biol Cell. 2014;25:1338–1354.
   PubMed Web of Science ®Google Scholar
• Jiang P, Nishimura T, Sakamaki Y, et al. The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17. Mol Biol Cell. 2014;25:1327–1337.
   PubMed Web of Science ®Google Scholar
• Solinger JA, Spang A. Tethering complexes in the endocytic pathway: CORVET and HOPS. FEBS J. 2013;280:2743–2757.
   PubMed Web of Science ®Google Scholar
• Orr A, Song H, Rusin SF, et al. HOPS catalyzes the interdependent assembly of each vacuolar SNARE into a SNARE complex. Mol Biol Cell. 2017;28:975–983.
   PubMed Web of Science ®Google Scholar
• McEwan DG, Popovic D, Gubas A, et al. PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins. Mol Cell. 2015;57:39–54.
   PubMed Web of Science ®Google Scholar
• Stroupe C, Collins KM, Fratti RA, et al. Purification of active HOPS complex reveals its affinities for phosphoinositides and the SNARE Vam7p. EMBO J. 2006;25:1579–1589.
   PubMed Web of Science ®Google Scholar
• Jia R, Guardia CM, Pu J, et al. BORC coordinates encounter and fusion of lysosomes with autophagosomes. Autophagy. 2017;13:1648–1663.
   PubMed Web of Science ®Google Scholar
• Schleinitz A, Pöttgen L-A, Keren-Kaplan T, et al. Consecutive functions of small GTPases guide HOPS-mediated tethering of late endosomes and lysosomes. Cell Rep. 2023;42:111969.
   PubMed Web of Science ®Google Scholar
• Baker RW, Jeffrey PD, Hughson FM. Crystal structures of the Sec1/Munc18 (SM) protein Vps33, alone and bound to the homotypic fusion and vacuolar protein sorting (HOPS) subunit Vps16*. PLoS One. 2013;8:e67409.
   PubMed Web of Science ®Google Scholar
• Graham SC, Wartosch L, Gray SR, et al. Structural basis of Vps33A recruitment to the human HOPS complex by Vps16. Proc Natl Acad Sci U S A. 2013;110:13345–13350.
   PubMed Web of Science ®Google Scholar
• Baker RW, Jeffrey PD, Zick M, et al. A direct role for the Sec1/Munc18-family protein Vps33 as a template for SNARE assembly. Science. 2015;349:1111–1114.
   PubMed Web of Science ®Google Scholar
• Behrmann H, Lürick A, Kuhlee A, et al. Structural identification of the Vps18 β-propeller reveals a critical role in the HOPS complex stability and function. J Biol Chem. 2014;289:33503–33512.
   PubMed Web of Science ®Google Scholar
• Bröcker C, Kuhlee A, Gatsogiannis C, et al. Molecular architecture of the multisubunit homotypic fusion and vacuole protein sorting (HOPS) tethering complex. Proc Natl Acad Sci U S A. 2012;109:1991–1996.
   PubMed Web of Science ®Google Scholar
• Chou H-T, Dukovski D, Chambers MG, et al. CATCHR, HOPS and CORVET tethering complexes share a similar architecture. Nat Struct Mol Biol. 2016;23:761–763.
   PubMed Web of Science ®Google Scholar
• Shvarev D, Schoppe J, König C, et al. Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery. Elife. 2022;11:e80901.
   PubMed Web of Science ®Google Scholar
• Zhang S, Tong M, Zheng D, et al. C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane tethering and fusion in mammalian autophagy. Nat Commun. 2023;14:6360.
   PubMed Web of Science ®Google Scholar
• Tian Y, Li Z, Hu W, et al. C. elegans screen identifies autophagy genes specific to multicellular organisms. Cell. 2010;141:1042–1055.
   PubMed Web of Science ®Google Scholar
• Wang Z, Miao G, Xue X, et al. The Vici syndrome protein EPG5 is a Rab7 effector that determines the fusion specificity of autophagosomes with late endosomes/lysosomes. Mol Cell. 2016;63:781–795.
   PubMed Web of Science ®Google Scholar
• Cullup T, Kho AL, Dionisi-Vici C, et al. Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy. Nat Genet. 2013;45:83–87.
   PubMed Web of Science ®Google Scholar
• Nam S-E, Cheung YW, Nguyen TN, et al. Insights on autophagosome-lysosome tethering from structural and biochemical characterization of human autophagy factor EPG5. Commun Biol. 2021;4:291.
   PubMed Web of Science ®Google Scholar
• Fan W, Nassiri A, Zhong Q. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). Proc Natl Acad Sci U S A. 2011;108:7769–7774.
   PubMed Web of Science ®Google Scholar
• Matsunaga K, Saitoh T, Tabata K, et al. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol. 2009;11:385–396.
   PubMed Web of Science ®Google Scholar
• Matsunaga K, Morita E, Saitoh T, et al. Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. J Cell Biol. 2010;190:511–521.
   PubMed Web of Science ®Google Scholar
• Itakura E, Kishi C, Inoue K, et al. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell. 2008;19:5360–5372.
   PubMed Web of Science ®Google Scholar
• Zhong Y, Wang QJ, Li X, et al. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol. 2009;11:468–476.
   PubMed Web of Science ®Google Scholar
• Sun Q, Fan W, Zhong Q. Regulation of Beclin 1 in autophagy. Autophagy. 2009;5:713–716.
   PubMed Web of Science ®Google Scholar
• Hamasaki M, Furuta N, Matsuda A, et al. Autophagosomes form at ER-mitochondria contact sites. Nature. 2013;495:389–393.
   PubMed Web of Science ®Google Scholar
• Chen D, Fan W, Lu Y, et al. A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate. Mol Cell. 2012;45:629–641.
   PubMed Web of Science ®Google Scholar
• Kim JH, Hong SB, Lee JK, et al. Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners. Autophagy. 2015;11:75–87.
   PubMed Web of Science ®Google Scholar
• Florey O. TECPR1 helps bridge the CASM during lysosome damage. EMBO J. 2023;42:e115210.
   PubMedGoogle Scholar
• Corkery DP, Castro-Gonzalez S, Knyazeva A, et al. An ATG12-ATG5-TECPR1 E3-like complex regulates unconventional LC3 lipidation at damaged lysosomes. EMBO Rep. 2023;24:e56841.
   PubMed Web of Science ®Google Scholar
• Boyle KB, Ellison CJ, Elliott PR, et al. TECPR1 conjugates LC3 to damaged endomembranes upon detection of sphingomyelin exposure. EMBO J. 2023;42:e113012.
   PubMed Web of Science ®Google Scholar
• Kaur N, de la Ballina LR, Haukaas HS, et al. TECPR1 is activated by damage-induced sphingomyelin exposure to mediate noncanonical autophagy. EMBO J. 2023;42:e113105.
   PubMed Web of Science ®Google Scholar
• Ebner P, Poetsch I, Deszcz L, et al. The IAP family member BRUCE regulates autophagosome-lysosome fusion. Nat Commun. 2018;9:599.
   PubMed Web of Science ®Google Scholar
• Marwaha R, Arya SB, Jagga D, et al. The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to lysosomes. J Cell Biol. 2017;216:1051–1070.
   PubMed Web of Science ®Google Scholar
• Shpilka T, Weidberg H, Pietrokovski S, et al. Atg8: an autophagy-related ubiquitin-like protein family. Genome Biol. 2011;12:226.
   PubMed Web of Science ®Google Scholar
• Tsuboyama K, Koyama-Honda I, Sakamaki Y, et al. The ATG conjugation systems are important for degradation of the inner autophagosomal membrane. Science. 2016;354:1036–1041.
   PubMed Web of Science ®Google Scholar
• Nakatogawa H, Ichimura Y, Ohsumi Y. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell. 2007;130:165–178.
   PubMed Web of Science ®Google Scholar
• Weidberg H, Shpilka T, Shvets E, et al. LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev Cell. 2011;20:444–454.
   PubMed Web of Science ®Google Scholar
• Nair U, Jotwani A, Geng J, et al. SNARE proteins are required for macroautophagy. Cell. 2011;146:290–302.
   PubMed Web of Science ®Google Scholar
• Yang A, Li Y, Pantoom S, et al. Semisynthetic lipidated LC3 protein mediates membrane fusion. Chembiochem. 2013;14:1296–1300.
   PubMed Web of Science ®Google Scholar
• Wu F, Watanabe Y, Guo XY, et al. Structural basis of the differential function of the two C. elegans Atg8 homologs, LGG-1 and LGG-2, in autophagy. Mol Cell. 2015;60:914–929.
   PubMed Web of Science ®Google Scholar
• Landajuela A, Hervás J, Antón Z, et al. Lipid geometry and bilayer curvature modulate LC3/GABARAP-mediated model autophagosomal elongation. Biophys J. 2016;110:411–422.
   PubMed Web of Science ®Google Scholar
• Hutagalung AH, Novick PJ. Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev. 2011;91:119–149.
   PubMed Web of Science ®Google Scholar
• Goody RS, Müller MP, Wu Y-W. Mechanisms of action of Rab proteins, key regulators of intracellular vesicular transport. Biol Chem. 2017;398:565–575.
   PubMed Web of Science ®Google Scholar
• Kuchitsu Y, Fukuda M. Revisiting Rab7 functions in mammalian autophagy: rab7 knockout studies. Cells. 2018;7:215.
   PubMed Web of Science ®Google Scholar
• Rak A, Pylypenko O, Niculae A, et al. Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease. Cell. 2004;117:749–760.
   PubMed Web of Science ®Google Scholar
• Wu M, Wang T, Loh E, et al. Structural basis for recruitment of RILP by small GTPase Rab7. EMBO J. 2005;24:1491–1501.
   PubMed Web of Science ®Google Scholar
• Blümer J, Rey J, Dehmelt L, et al. RabGEFs are a major determinant for specific Rab membrane targeting. J Cell Biol. 2013;200:287–300.
   PubMed Web of Science ®Google Scholar
• Müller MP, Goody RS. Molecular control of Rab activity by GEFs, GAPs and GDI. Small GTPases. 2018;9:5–21.
   PubMedGoogle Scholar
• Borchers A-C, Langemeyer L, Ungermann C. Who’s in control? Principles of Rab GTPase activation in endolysosomal membrane trafficking and beyond. J Cell Biol. 2021;220:e202105120.
   PubMed Web of Science ®Google Scholar
• Gao J, Langemeyer L, Kümmel D, et al. Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre-autophagosomal structure. Elife. 2018;7:e31145.
   PubMed Web of Science ®Google Scholar
• Kiontke S, Langemeyer L, Kuhlee A, et al. Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1-Ccz1. Nat Commun. 2017;8:14034.
   PubMed Web of Science ®Google Scholar
• Klink BU, Herrmann E, Antoni C, et al. Structure of the Mon1-Ccz1 complex reveals molecular basis of membrane binding for Rab7 activation. Proc Natl Acad Sci U S A. 2022;119:e2121494119.
   PubMed Web of Science ®Google Scholar
• Herrmann E, Schäfer J-H, Wilmes S, et al. Structure of the metazoan Rab7 GEF complex Mon1-Ccz1-Bulli. Proc Natl Acad Sci U S A. 2023;120:e2301908120.
   PubMed Web of Science ®Google Scholar
• Yong X, Jia G, Liu Z, et al. Cryo-EM structure of the Mon1-Ccz1-RMC1 complex reveals molecular basis of metazoan RAB7A activation. Proc Natl Acad Sci U S A. 2023;120:e2301725120.
   PubMed Web of Science ®Google Scholar