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. 2010 Nov 9;1(10):907–915. doi: 10.1007/s13238-010-0121-z

The late stage of autophagy: cellular events and molecular regulation

Jingjing Tong 1,2, Xianghua Yan 2, Li Yu 1,✉
PMCID: PMC4875124  PMID: 21204017

Abstract

Autophagy is an intracellular degradation system that delivers cytoplasmic contents to the lysosome for degradation. It is a “self-eating” process and plays a “house-cleaner” role in cells. The complex process consists of several sequential steps—induction, autophagosome formation, fusion of lysosome and autophagosome, degradation, efflux transportation of degradation products, and autophagic lysosome reformation. In this review, the cellular and molecular regulations of late stage of autophagy, including cellular events after fusion step, are summarized.

Keywords: autophagy, autophagosome, lysosome, fusion, degradation

References

  1. Aplin A., Jasionowski T., Tuttle D.L., Lenk S.E., Dunn W.A., Jr. Cytoskeletal elements are required for the formation and maturation of autophagic vacuoles. J Cell Physiol. 1992;152:458–466. doi: 10.1002/jcp.1041520304. [DOI] [PubMed] [Google Scholar]
  2. Atlashkin V., Kreykenbohm V., Eskelinen E.-L., Wenzel D., Fayyazi A., Fischer von Mollard G. Deletion of the SNARE vti1b in mice results in the loss of a single SNARE partner, syntaxin 8. Mol Cell Biol. 2003;23:5198–5207. doi: 10.1128/MCB.23.15.5198-5207.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Axe E.L., Walker S.A., Manifava M., Chandra P., Roderick H.L., Habermann A., Griffiths G., Ktistakis N.T. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008;182:685–701. doi: 10.1083/jcb.200803137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bache K.G., Raiborg C., Mehlum A., Madshus I.H., Stenmark H. Phosphorylation of Hrs downstream of the epidermal growth factor receptor. Eur J Biochem. 2002;269:3881–3887. doi: 10.1046/j.1432-1033.2002.03046.x. [DOI] [PubMed] [Google Scholar]
  5. Block M.R., Glick B.S., Wilcox C.A., Wieland F.T., Rothman J. E. Purification of an N-ethylmaleimide-sensitive protein catalyzing vesicular transport. Proc Natl Acad Sci U S A. 1988;85:7852–7856. doi: 10.1073/pnas.85.21.7852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cai H., Reinisch K., Ferro-Novick S. Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev Cell. 2007;12:671–682. doi: 10.1016/j.devcel.2007.04.005. [DOI] [PubMed] [Google Scholar]
  7. Callebaut I., de Gunzburg J., Goud B., Mornon J.P. RUN domains: a new family of domains involved in Ras-like GTPase signaling. Trends Biochem Sci. 2001;26:79–83. doi: 10.1016/s0968-0004(00)01730-8. [DOI] [PubMed] [Google Scholar]
  8. Cao X., Barlowe C. Asymmetric requirements for a Rab GTPase and SNARE proteins in fusion of COPII vesicles with acceptor membranes. J Cell Biol. 2000;149:55–66. doi: 10.1083/jcb.149.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crighton D., Wilkinson S., O’Prey J., Syed N., Smith P., Harrison P.R., Gasco M., Garrone O., Crook T., Ryan K.M. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 2006;126:121–134. doi: 10.1016/j.cell.2006.05.034. [DOI] [PubMed] [Google Scholar]
  10. Darsow T., Rieder S.E., Emr S.D. A multispecificity syntaxin homologue, Vam3p, essential for autophagic and biosynthetic protein transport to the vacuole. J Cell Biol. 1997;138:517–529. doi: 10.1083/jcb.138.3.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dulubova I., Yamaguchi T., Wang Y., Südhof T.C., Rizo J. Vam3p structure reveals conserved and divergent properties of syntaxins. Nat Struct Biol. 2001;8:258–264. doi: 10.1038/85012. [DOI] [PubMed] [Google Scholar]
  12. Egami Y., Kiryu-Seo S., Yoshimori T., Kiyama H. Induced expressions of Rab24 GTPase and LC3 in nerve-injured motor neurons. Biochem Biophys Res Commun. 2005;337:1206–1213. doi: 10.1016/j.bbrc.2005.09.171. [DOI] [PubMed] [Google Scholar]
  13. Epple U.D., Suriapranata I., Eskelinen E.-L., Thumm M. Aut5/Cvt17p, a putative lipase essential for disintegration of autophagic bodies inside the vacuole. J Bacteriol. 2001;183:5942–5955. doi: 10.1128/JB.183.20.5942-5955.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Epple U.D., Eskelinen E.L., Thumm M. Intravacuolar membrane lysis in Saccharomyces cerevisiae. Does vacuolar targeting of Cvt17/Aut5p affect its function? J Biol Chem. 2003;278:7810–7821. doi: 10.1074/jbc.M209309200. [DOI] [PubMed] [Google Scholar]
  15. Eskelinen E.L. Maturation of autophagic vacuoles in mammalian cells. Autophagy. 2005;1:1–10. doi: 10.4161/auto.1.1.1270. [DOI] [PubMed] [Google Scholar]
  16. Eskelinen E.L., Tanaka Y., Saftig P. At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol. 2003;13:137–145. doi: 10.1016/s0962-8924(03)00005-9. [DOI] [PubMed] [Google Scholar]
  17. Eskelinen E.L., Schmidt C.K., Neu S., Willenborg M., Fuertes G., Salvador N., Tanaka Y., Lüllmann-Rauch R., Hartmann D., Heeren J., et al. Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts. Mol Biol Cell. 2004;15:3132–3145. doi: 10.1091/mbc.E04-02-0103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fader C.M., Sánchez D., Furlán M., Colombo M.I. Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells. Traffic. 2008;9:230–250. doi: 10.1111/j.1600-0854.2007.00677.x. [DOI] [PubMed] [Google Scholar]
  19. Fass E., Shvets E., Degani I., Hirschberg K., Elazar Z. Microtubules support production of starvation-induced autophagosomes but not their targeting and fusion with lysosomes. J Biol Chem. 2006;281:36303–36316. doi: 10.1074/jbc.M607031200. [DOI] [PubMed] [Google Scholar]
  20. Gasch A.P., Spellman P.T., Kao C.M., Carmel-Harel O., Eisen M. B., Storz G., Botstein D., Brown P.O. Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell. 2000;11:4241–4257. doi: 10.1091/mbc.11.12.4241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gill S.R., Schroer T.A., Szilak I., Steuer E.R., Sheetz M.P., Cleveland D.W. Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein. J Cell Biol. 1991;115:1639–1650. doi: 10.1083/jcb.115.6.1639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gutierrez M.G., Munafó D.B., Berón W., Colombo M.I. Rab7 is required for the normal progression of the autophagic pathway in mammalian cells. J Cell Sci. 2004;117:2687–2697. doi: 10.1242/jcs.01114. [DOI] [PubMed] [Google Scholar]
  23. Hamasaki M., Yoshimori T. Where do they come from? Insight into autophagosome formation. FEBS Lett. 2010;584:1296–1301. doi: 10.1016/j.febslet.2010.02.061. [DOI] [PubMed] [Google Scholar]
  24. Hayakawa A., Hayes S.J., Lawe D.C., Sudharshan E., Tuft R., Fogarty K., Lambright D., Corvera S. Structural basis for endosomal targeting by FYVE domains. J Biol Chem. 2004;279:5958–5966. doi: 10.1074/jbc.M310503200. [DOI] [PubMed] [Google Scholar]
  25. Huynh K.K., Eskelinen E.L., Scott C.C., Malevanets A., Saftig P., Grinstein S. LAMP proteins are required for fusion of lysosomes with phagosomes. EMBO J. 2007;26:313–324. doi: 10.1038/sj.emboj.7601511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Itoh T., Fujita N., Kanno E., Yamamoto A., Yoshimori T., Fukuda M. Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation. Mol Biol Cell. 2008;19:2916–2925. doi: 10.1091/mbc.E07-12-1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Jäger S., Bucci C., Tanida I., Ueno T., Kominami E., Saftig P., Eskelinen E.L. Role for Rab7 in maturation of late autophagic vacuoles. J Cell Sci. 2004;117:4837–4848. doi: 10.1242/jcs.01370. [DOI] [PubMed] [Google Scholar]
  28. Jahn R., Scheller R.H. SNAREs—engines for membrane fusion. Nat Rev Mol Cell Biol. 2006;7:631–643. doi: 10.1038/nrm2002. [DOI] [PubMed] [Google Scholar]
  29. Jahreiss L., Menzies F.M., Rubinsztein D.C. The itinerary of autophagosomes: from peripheral formation to kiss-and-run fusion with lysosomes. Traffic. 2008;9:574–587. doi: 10.1111/j.1600-0854.2008.00701.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kanazawa C., Morita E., Yamada M., Ishii N., Miura S., Asao H., Yoshimori T., Sugamura K. Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation. Biochem Biophys Res Commun. 2003;309:848–856. doi: 10.1016/j.bbrc.2003.08.078. [DOI] [PubMed] [Google Scholar]
  31. Kimura S., Noda T., Yoshimori T. Dynein-dependent movement of autophagosomes mediates efficient encounters with lysosomes. Cell Struct Funct. 2008;33:109–122. doi: 10.1247/csf.08005. [DOI] [PubMed] [Google Scholar]
  32. Klionsky D.J. The molecular machinery of autophagy: unanswered questions. J Cell Sci. 2005;118:7–18. doi: 10.1242/jcs.01620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Klionsky D.J. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 2007;8:931–937. doi: 10.1038/nrm2245. [DOI] [PubMed] [Google Scholar]
  34. Kouno T., Mizuguchi M., Tanida I., Ueno T., Kanematsu T., Mori Y., Shinoda H., Hirata M., Kominami E., Kawano K. Solution structure of microtubule-associated protein light chain 3 and identification of its functional subdomains. J Biol Chem. 2005;280:24610–24617. doi: 10.1074/jbc.M413565200. [DOI] [PubMed] [Google Scholar]
  35. Kucharczyk R., Dupre S., Avaro S., Haguenauer-Tsapis R., Słonimski P.P., Rytka J. The novel protein Ccz1p required for vacuolar assembly in Saccharomyces cerevisiae functions in the same transport pathway as Ypt7p. J Cell Sci. 2000;113:4301–4311. doi: 10.1242/jcs.113.23.4301. [DOI] [PubMed] [Google Scholar]
  36. Kucharczyk R., Kierzek A.M., Slonimski P.P., Rytka J. The Ccz1 protein interacts with Ypt7 GTPase during fusion of multiple transport intermediates with the vacuole in S. cerevisiae. J Cell Sci. 2001;114:3137–3145. doi: 10.1242/jcs.114.17.3137. [DOI] [PubMed] [Google Scholar]
  37. Kutateladze T.G. Phosphatidylinositol 3-phosphate recognition and membrane docking by the FYVE domain. Biochim Biophys Acta. 2006;1761:868–877. doi: 10.1016/j.bbalip.2006.03.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lakadamyali M., Rust M.J., Babcock H.P., Zhuang X. Visualizing infection of individual influenza viruses. Proc Natl Acad Sci U S A. 2003;100:9280–9285. doi: 10.1073/pnas.0832269100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Langosch D., Hofmann M., Ungermann C. The role of transmembrane domains in membrane fusion. Cell Mol Life Sci. 2007;64:850–864. doi: 10.1007/s00018-007-6439-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lee J.A., Beigneux A., Ahmad S.T., Young S.G., Gao F.B. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr Biol. 2007;17:1561–1567. doi: 10.1016/j.cub.2007.07.029. [DOI] [PubMed] [Google Scholar]
  41. Liang C., Feng P., Ku B., Dotan I., Canaani D., Oh B.H., Jung J.U. Autophagic and tumour suppressor activity of a novel Beclin 1-binding protein UVRAG. Nat Cell Biol. 2006;8:688–699. doi: 10.1038/ncb1426. [DOI] [PubMed] [Google Scholar]
  42. Liang C., Feng P., Ku B., Oh B.H., Jung J.U., Oh B., Jung J. UVRAG: a new player in autophagy and tumor cell growth. Autophagy. 2007;3:69–71. doi: 10.4161/auto.3437. [DOI] [PubMed] [Google Scholar]
  43. Liang C., Lee J.S., Inn K.S., Gack M.U., Li Q., Roberts E.A., Vergne I., Deretic V., Feng P., Akazawa C., et al. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol. 2008;10:776–787. doi: 10.1038/ncb1740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Liang C., Sir D., Lee S., Ou J.H., Jung J.U. Beyond autophagy: the role of UVRAG in membrane trafficking. Autophagy. 2008;4:817–820. doi: 10.4161/auto.6496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Lindmo K., Simonsen A., Brech A., Finley K., Rusten T.E., Stenmark H. A dual function for Deep orange in programmed autophagy in the Drosophila melanogaster fat body. Exp Cell Res. 2006;312:2018–2027. doi: 10.1016/j.yexcr.2006.03.002. [DOI] [PubMed] [Google Scholar]
  46. Lloyd J.B. Metabolite efflux and influx across the lysosome membrane. Subcell Biochem. 1996;27:361–386. doi: 10.1007/978-1-4615-5833-0_11. [DOI] [PubMed] [Google Scholar]
  47. Lloyd T.E., Atkinson R., Wu M.N., Zhou Y., Pennetta G., Bellen H.J. Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell. 2002;108:261–269. doi: 10.1016/s0092-8674(02)00611-6. [DOI] [PubMed] [Google Scholar]
  48. Longatti A., Tooze S.A. Vesicular trafficking and autophagosome formation. Cell Death Differ. 2009;16:956–965. doi: 10.1038/cdd.2009.39. [DOI] [PubMed] [Google Scholar]
  49. Lupas A., Van Dyke M., Stock J. Predicting coiled coils from protein sequences. Science. 1991;252:1162–1164. doi: 10.1126/science.252.5009.1162. [DOI] [PubMed] [Google Scholar]
  50. Mann S.S., Hammarback J.A. Molecular characterization of light chain 3. A microtubule binding subunit of MAP1A and MAP1B. J Biol Chem. 1994;269:11492–11497. [PubMed] [Google Scholar]
  51. Marchler-Bauer A., Anderson J.B., Chitsaz F., Derbyshire M.K., DeWeese-Scott C., Fong J.H., Geer L.Y., Geer R.C., Gonzales N.R., Gwadz M., et al. CDD: specific functional annotation with the Conserved Domain Database. Nucleic Acids Res. 2009;37:D205–D210. doi: 10.1093/nar/gkn845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Marino Z., Heidi M. Rab proteins as membrane prganizers. Natl Rev. 2001;2:107–118. doi: 10.1038/35052055. [DOI] [PubMed] [Google Scholar]
  53. Mechler B., Wolf D.H. Analysis of proteinase A function in yeast. Eur J Biochem. 1981;121:47–52. doi: 10.1111/j.1432-1033.1981.tb06427.x. [DOI] [PubMed] [Google Scholar]
  54. Mehrpour M., Esclatine A., Beau I., Codogno P. Overview of macroautophagy regulation in mammalian cells. Cell Res. 2010;20:748–762. doi: 10.1038/cr.2010.82. [DOI] [PubMed] [Google Scholar]
  55. Mesa R., Salomón C., Roggero M., Stahl P.D., Mayorga L.S. Rab22a affects the morphology and function of the endocytic pathway. J Cell Sci. 2001;114:4041–4049. doi: 10.1242/jcs.114.22.4041. [DOI] [PubMed] [Google Scholar]
  56. Mima J., Hickey C.M., Xu H., Jun Y., Wickner W. Reconstituted membrane fusion requires regulatory lipids, SNAREs and synergistic SNARE chaperones. EMBO J. 2008;27:2031–2042. doi: 10.1038/emboj.2008.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Mizushima N. Autophagy: process and function. Genes Dev. 2007;21:2861–2873. doi: 10.1101/gad.1599207. [DOI] [PubMed] [Google Scholar]
  58. Munafó D.B., Colombo M.I. Induction of autophagy causes dramatic changes in the subcellular distribution of GFPRab24. Traffic. 2002;3:472–482. doi: 10.1034/j.1600-0854.2002.30704.x. [DOI] [PubMed] [Google Scholar]
  59. Nakamura N., Matsuura A., Wada Y., Ohsumi Y. Acidification of vacuoles is required for autophagic degradation in the yeast, Saccharomyces cerevisiae. J Biochem. 1997;121:338–344. doi: 10.1093/oxfordjournals.jbchem.a021592. [DOI] [PubMed] [Google Scholar]
  60. Nakatogawa H., Suzuki K., Kamada Y., Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol. 2009;10:458–467. doi: 10.1038/nrm2708. [DOI] [PubMed] [Google Scholar]
  61. Nara A., Mizushima N., Yamamoto A., Kabeya Y., Ohsumi Y., Yoshimori T. SKD1 AAA ATPase-dependent endosomal transport is involved in autolysosome formation. Cell Struct Funct. 2002;27:29–37. doi: 10.1247/csf.27.29. [DOI] [PubMed] [Google Scholar]
  62. Nichols B.J., Ungermann C., Pelham H.R.B., Wickner W.T., Haas A. Homotypic vacuolar fusion mediated by t- and v- SNAREs. Nature. 1997;387:199–202. doi: 10.1038/387199a0. [DOI] [PubMed] [Google Scholar]
  63. Novick P., Zerial M. The diversity of Rab proteins in vesicle transport. Curr Opin Cell Biol. 1997;9:496–504. doi: 10.1016/s0955-0674(97)80025-7. [DOI] [PubMed] [Google Scholar]
  64. Odorizzi G., Babst M., Emr S.D. Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell. 1998;95:847–858. doi: 10.1016/s0092-8674(00)81707-9. [DOI] [PubMed] [Google Scholar]
  65. Odorizzi G., Babst M., Emr S.D. Phosphoinositide signaling and the regulation of membrane trafficking in yeast. Trends Biochem Sci. 2000;25:229–235. doi: 10.1016/s0968-0004(00)01543-7. [DOI] [PubMed] [Google Scholar]
  66. Olkkonen V.M., Dupree P., Killisch I., Lütcke A., Zerial M., Simons K. Molecular cloning and subcellular localization of three GTP-binding proteins of the rab subfamily. J Cell Sci. 1993;106:1249–1261. doi: 10.1242/jcs.106.4.1249. [DOI] [PubMed] [Google Scholar]
  67. Pankiv S., Alemu E.A., Brech A., Bruun J.A., Lamark T., Overvatn A., Bjørkøy G., Johansen T. FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus enddirected vesicle transport. J Cell Biol. 2010;188:253–269. doi: 10.1083/jcb.200907015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Parlati F., McNew J.A., Fukuda R., Miller R., Söllner T.H., Rothman J.E. Topological restriction of SNARE-dependent membrane fusion. Nature. 2000;407:194–198. doi: 10.1038/35025076. [DOI] [PubMed] [Google Scholar]
  69. Parr C.L., Keates R.A., Bryksa B.C., Ogawa M., Yada R.Y. The structure and function of Saccharomyces cerevisiae proteinase A. Yeast. 2007;24:467–480. doi: 10.1002/yea.1485. [DOI] [PubMed] [Google Scholar]
  70. Peplowska K., Cabrera M., Ungermann C. UVRAG reveals its second nature. Nat Cell Biol. 2008;10:759–761. doi: 10.1038/ncb0708-759. [DOI] [PubMed] [Google Scholar]
  71. Price A., Seals D., Wickner W., Ungermann C. The docking stage of yeast vacuole fusion requires the transfer of proteins from a cis-SNARE complex to a Rab/Ypt protein. J Cell Biol. 2000;148:1231–1238. doi: 10.1083/jcb.148.6.1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Price A., Wickner W., Ungermann C. Proteins needed for vesicle budding from the Golgi complex are also required for the docking step of homotypic vacuole fusion. J Cell Biol. 2000;148:1223–1229. doi: 10.1083/jcb.148.6.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Pulipparacharuvil S., Akbar M.A., Ray S., Sevrioukov E.A., Haberman A.S., Rohrer J., Krämer H. Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules. J Cell Sci. 2005;118:3663–3673. doi: 10.1242/jcs.02502. [DOI] [PubMed] [Google Scholar]
  74. Raiborg C., Stenmark H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature. 2009;458:445–452. doi: 10.1038/nature07961. [DOI] [PubMed] [Google Scholar]
  75. Ravikumar B., Acevedo-Arozena A., Imarisio S., Berger Z., Vacher C., O’Kane C.J., Brown S.D., Rubinsztein D.C. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat Genet. 2005;37:771–776. doi: 10.1038/ng1591. [DOI] [PubMed] [Google Scholar]
  76. Ravikumar B., Futter M., Jahreiss L., Korolchuk V.I., Lichtenberg M., Luo S., Massey D.C., Menzies F.M., Narayanan U., Renna M., et al. Mammalian macroautophagy at a glance. J Cell Biol. 2009;122:1707–1711. doi: 10.1242/jcs.031773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Recacha R., Boulet A., Jollivet F., Monier S., Houdusse A., Goud B., Khan A.R. Structural basis for recruitment of Rab6-interacting protein 1 to Golgi via a RUN domain. Structure. 2009;17:21–30. doi: 10.1016/j.str.2008.10.014. [DOI] [PubMed] [Google Scholar]
  78. Rieder S.E., Emr S.D. A novel RING finger protein complex essential for a late step in protein transport to the yeast vacuole. Mol Biol Cell. 1997;8:2307–2327. doi: 10.1091/mbc.8.11.2307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Rothman J.E. Mechanisms of intracellular protein transport. Nature. 1994;372:55–63. doi: 10.1038/372055a0. [DOI] [PubMed] [Google Scholar]
  80. Rothman J.E., Wieland F.T. Protein sorting by transport vesicles. Science. 1996;272:227–234. doi: 10.1126/science.272.5259.227. [DOI] [PubMed] [Google Scholar]
  81. Rusten T.E., Stenmark H. How do ESCRT proteins control autophagy? J Cell Sci. 2009;122:2179–2183. doi: 10.1242/jcs.050021. [DOI] [PubMed] [Google Scholar]
  82. Rusten T.E., Vaccari T., Lindmo K., Rodahl L.M., Nezis I.P., Sem-Jacobsen C., Wendler F., Vincent J.P., Brech A., Bilder D., et al. ESCRTs and Fab1 regulate distinct steps of autophagy. Curr Biol. 2007;17:1817–1825. doi: 10.1016/j.cub.2007.09.032. [DOI] [PubMed] [Google Scholar]
  83. Saftig P., Beertsen W., Eskelinen E.L. LAMP-2: a control step for phagosome and autophagosome maturation. Autophagy. 2008;4:510–512. doi: 10.4161/auto.5724. [DOI] [PubMed] [Google Scholar]
  84. Sato T.K., Darsow T., Emr S.D. Vam7p, a SNAP-25-like molecule, and Vam3p, a syntaxin homolog, function together in yeast vacuolar protein trafficking. Mol Cell Biol. 1998;18:5308–5319. doi: 10.1128/mcb.18.9.5308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Sato T.K., Rehling P., Peterson M.R., Emr S.D. Class C Vps protein complex regulates vacuolar SNARE pairing and is required for vesicle docking/fusion. Mol Cell. 2000;6:661–671. doi: 10.1016/s1097-2765(00)00064-2. [DOI] [PubMed] [Google Scholar]
  86. Satoh A.K., O’Tousa J.E., Ozaki K., Ready D.F. Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors. Development. 2005;132:1487–1497. doi: 10.1242/dev.01704. [DOI] [PubMed] [Google Scholar]
  87. Schroer T.A., Sheetz M.P. Two activators of microtubulebased vesicle transport. J Cell Biol. 1991;115:1309–1318. doi: 10.1083/jcb.115.5.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Seals D.F., Eitzen G., Margolis N., Wickner W.T., Price A. A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion. Proc Natl Acad Sci U S A. 2000;97:9402–9407. doi: 10.1073/pnas.97.17.9402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Seglen P.O., Berg T.O., Blankson H., Fengsrud M., Holen I., Strømhaug P.E. Structural aspects of autophagy. Adv Exp Med Biol. 1996;389:103–111. doi: 10.1007/978-1-4613-0335-0_12. [DOI] [PubMed] [Google Scholar]
  90. Shirahama K., Noda T., Ohsumi Y. Mutational analysis of Csc1/Vps4p: involvement of endosome in regulation of autophagy in yeast. Cell Struct Funct. 1997;22:501–509. doi: 10.1247/csf.22.501. [DOI] [PubMed] [Google Scholar]
  91. Söllner T., Bennett M.K., Whiteheart S.W., Scheller R.H., Rothman J.E. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell. 1993;75:409–418. doi: 10.1016/0092-8674(93)90376-2. [DOI] [PubMed] [Google Scholar]
  92. Somsel Rodman J., Wandinger-Ness A. Rab GTPases coordinate endocytosis. J Cell Sci. 2000;113:183–192. doi: 10.1242/jcs.113.2.183. [DOI] [PubMed] [Google Scholar]
  93. Stroupe C., Collins K.M., Fratti R.A., Wickner W. Purification of active HOPS complex reveals its affinities for phosphoinositides and the SNARE Vam7p. EMBO J. 2006;25:1579–1589. doi: 10.1038/sj.emboj.7601051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Sugawara K., Suzuki N.N., Fujioka Y., Mizushima N., Ohsumi Y., Inagaki F. The crystal structure of microtubuleassociated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8. Genes Cells. 2004;9:611–618. doi: 10.1111/j.1356-9597.2004.00750.x. [DOI] [PubMed] [Google Scholar]
  95. Suriapranata I., Epple U.D., Bernreuther D., Bredschneider M., Sovarasteanu K., Thumm M. The breakdown of autophagic vesicles inside the vacuole depends on Aut4p. J Cell Sci. 2000;113:4025–4033. doi: 10.1242/jcs.113.22.4025. [DOI] [PubMed] [Google Scholar]
  96. Takahashi Y., Coppola D., Matsushita N., Cualing H.D., Sun M., Sato Y., Liang C., Jung J.U., Cheng J.Q., Mulé J.J., et al. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol. 2007;9:1142–1151. doi: 10.1038/ncb1634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Takahashi Y., Meyerkord C.L., Wang H.G. BARgaining membranes for autophagosome formation: Regulation of autophagy and tumorigenesis by Bif-1/Endophilin B1. Autophagy. 2008;4:121–124. doi: 10.4161/auto.5265. [DOI] [PubMed] [Google Scholar]
  98. Takeshige K., Baba M., Tsuboi S., Noda T., Ohsumi Y. Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol. 1992;119:301–311. doi: 10.1083/jcb.119.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Tamai K., Tanaka N., Nara A., Yamamoto A., Nakagawa I., Yoshimori T., Ueno Y., Shimosegawa T., Sugamura K. Role of Hrs in maturation of autophagosomes in mammalian cells. Biochem Biophys Res Commun. 2007;360:721–727. doi: 10.1016/j.bbrc.2007.06.105. [DOI] [PubMed] [Google Scholar]
  100. Tanaka Y., Guhde G., Suter A., Eskelinen E.L., Hartmann D., Lüllmann-Rauch R., Janssen P.M., Blanz J., von Figura K., Saftig P. Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature. 2000;406:902–906. doi: 10.1038/35022595. [DOI] [PubMed] [Google Scholar]
  101. Teter S.A., Eggerton K.P., Scott S.V., Kim J., Fischer A.M., Klionsky D.J. Degradation of lipid vesicles in the yeast vacuole requires function of Cvt17, a putative lipase. J Biol Chem. 2001;276:2083–2087. doi: 10.1074/jbc.C000739200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Ungermann C., Langosch D. Functions of SNAREs in intracellular membrane fusion and lipid bilayer mixing. J Cell Sci. 2005;118:3819–3828. doi: 10.1242/jcs.02561. [DOI] [PubMed] [Google Scholar]
  103. Ungermann C., Nichols B.J., Pelham H.R.B., Wickner W. A vacuolar v-t-SNARE complex, the predominant form in vivo and on isolated vacuoles, is disassembled and activated for docking and fusion. J Cell Biol. 1998;140:61–69. doi: 10.1083/jcb.140.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Ungermann C., von Mollard G.F., Jensen O.N., Margolis N., Stevens T.H., Wickner W. Three v-SNAREs and two t- SNAREs, present in a pentameric cis-SNARE complex on isolated vacuoles, are essential for homotypic fusion. J Cell Biol. 1999;145:1435–1442. doi: 10.1083/jcb.145.7.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Ungermann C., Wickner W. Vam7p, a vacuolar SNAP-25 homolog, is required for SNARE complex integrity and vacuole docking and fusion. EMBO J. 1998;17:3269–3276. doi: 10.1093/emboj/17.12.3269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Wang C.-W., Klionsky D.J. The molecular mechanism of autophagy. Mol Med. 2003;9:65–76. [PMC free article] [PubMed] [Google Scholar]
  107. Wang C.-W., Stromhaug P.E., Kauffman E.J., Weisman L.S., Klionsky D.J. Yeast homotypic vacuole fusion requires the Ccz1-Mon1 complex during the tethering/docking stage. J Cell Biol. 2003;163:973–985. doi: 10.1083/jcb.200308071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Wang C.-W., Stromhaug P.E., Shima J., Klionsky D.J. The Ccz1-Mon1 protein complex is required for the late step of multiple vacuole delivery pathways. J Biol Chem. 2002;277:47917–47927. doi: 10.1074/jbc.M208191200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  109. Weber T., Zemelman B.V., McNew J.A., Westermann B., Gmachl M., Parlati F., Söllner T.H., Rothman J.E. SNAR-Epins: minimal machinery for membrane fusion. Cell. 1998;92:759–772. doi: 10.1016/s0092-8674(00)81404-x. [DOI] [PubMed] [Google Scholar]
  110. White S.R., Lauring B. AAA + ATPases: achieving diversity of function with conserved machinery. Traffic. 2007;8:1657–1667. doi: 10.1111/j.1600-0854.2007.00642.x. [DOI] [PubMed] [Google Scholar]
  111. Wurmser A.E., Sato T.K., Emr S.D. component of the vacuolar class C-Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent docking and fusion. J Cell Biol. 2000;151:551–62. doi: 10.1083/jcb.151.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Xie Z., Klionsky D.J. Autophagosome formation: core machinery and adaptations. Nat Cell Biol. 2007;9:1102–1109. doi: 10.1038/ncb1007-1102. [DOI] [PubMed] [Google Scholar]
  113. Xu H., Jun Y., Thompson J., Yates J., Wickner W. HOPS prevents the disassembly of trans-SNARE complexes by Sec17p/Sec1p during membrane fusion. J EMBO. 2010;29:1948–1960. doi: 10.1038/emboj.2010.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  114. Yang Z., Huang J., Geng J., Nair U., Klionsky D.J. Atg22 recycles amino acids to link the degradative and recycling functions of autophagy. Mol Biol Cell. 2006;17:5094–5104. doi: 10.1091/mbc.E06-06-0479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  115. Yorimitsu T., Klionsky D.J. Autophagy: molecular machinery for self-eating. Cell Death Differ. 2005;12:1542–1552. doi: 10.1038/sj.cdd.4401765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Yu L., McPhee C.K., Zheng L., Mardones G.A., Rong Y., Peng J., Mi N., Zhao Y., Liu Z., Wan F., et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 2010;17:942–946. doi: 10.1038/nature09076. [DOI] [PMC free article] [PubMed] [Google Scholar]

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