Regulation of autophagy by amino acid availability in S. cerevisiae and mammalian cells

Amino Acids

Volumn 47, Issue 10, 2015, Pages 2165-2175

  Abeliovich, Hagai ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Amino acids; Autophagy; Macroautophagy; Microautophagy; Nitrogen starvation; Tor

Indexed keywords

AMINO ACID; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; NITROGEN; TARGET OF RAPAMYCIN KINASE; UBIQUITIN;

AUTOPHAGY; CELL FUNCTION; CELL MEMBRANE; CELL VIABILITY; CHAPERONE-MEDIATED AUTOPHAGY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; INTRACELLULAR SPACE; MACROAUTOPHAGY; MAMMAL; MAMMAL CELL; NONHUMAN; NUTRIENT; NUTRIENT AVAILABILITY; OXIDATIVE STRESS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION; YEAST; YEAST CELL; ANIMAL; HUMAN; METABOLISM;

AMINO ACIDS; ANIMALS; AUTOPHAGY; HUMANS; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION;

EID: 84942500585     PISSN: 09394451     EISSN: 14382199     Source Type: Journal    
DOI: 10.1007/s00726-014-1787-y     Document Type: Review

References (122)

1. Abeliovich H, Darsow T, Emr SD (1999) Cytoplasm to vacuole trafficking of aminopeptidase I requires a t-SNARE-Sec1p complex composed of Tlg2p and Vps45p. EMBO J 18:6005-6016
2. Abeliovich H, Dunn WAJ, Kim J, Klionsky DJ (2000) Dissection of autophagosome biogenesis into distinct nucleation and expansion steps. J Cell Biol 151:1025-1034
3. Abeliovich H, Zhang C, Dunn WAJ, Shokat KM, Klionsky DJ (2003) Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy. Mol Biol Cell 14:477-490
4. Alvarez B, Moreno S (2006) Fission yeast Tor2 promotes cell growth and represses cell differentiation. J Cell Sci 119:4475-4485
5. Ashford TP, Porter KR (1962) Cytoplasmic components in hepatic cell lysosomes. J Cell Biol 12:198-202
6. 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
7. Baba M, Takeshige K, Baba N, Ohsumi Y (1994) Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization. J Cell Biol 124:903-913
8. Bandyopadhyay U, Kaushik S, Varticovski L, Cuervo AM (2008) The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Mol Cell Biol 28:5747-5763
9. Barbet NC, Schneider U, Helliwell SB, Stansfield I, Tuite MF, Hall MN (1996) TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell 7:25-42
10. Berg TO, Fengsrud M, Stromhaug PE, Berg T, Seglen PO (1998) Isolation and characterization of rat liver amphisomes. Evidence for fusion of autophagosomes with both early and late endosomes. J Biol Chem 273:21883-21892
11. Binda M, Peli-Gulli MP, Bonfils G, Panchaud N, Urban J, Sturgill TW, Loewith R, De Virgilio C (2009) The Vam6 GEF controls TORC1 by activating the EGO complex. Mol Cell 35:563-573
12. Chiang HL, Terlecky SR, Plant CP, Dice JF (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246:382-385
13. Cuervo AM, Dice JF (1996) A receptor for the selective uptake and degradation of proteins by lysosomes. Science 273:501-503
14. Cuervo AM, Dice JF (2000) Age-related decline in chaperone-mediated autophagy. J Biol Chem 275:31505-31513
15. Cuervo AM, Knecht E, Terlecky SR, Dice JF (1995) Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation. Am J Physiol 269:C1200-C1208
16. Cuervo AM, Dice JF, Knecht E (1997) A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins. J Biol Chem 272:5606-5615
17. Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D (2004) Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305:1292-1295
18. Darsow T, Rieder SE, Emr SD (1997) A multispecificity syntaxin homologue, Vam3p, essential for autophagic and biosynthetic protein transport to the vacuole. J Cell Biol 138:517-529
19. Deter RL, De Duve C (1967) Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. J Cell Biol 33:437-449
20. Dever TE, Feng L, Wek RC, Cigan AM, Donahue TF, Hinnebusch AG (1992) Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast. Cell 68:585-596
21. Dice JF (1987) Molecular determinants of protein half-lives in eukaryotic cells. FASEB J 1:349-357
22. Dice JF (1992) Selective degradation of cytosolic proteins by lysosomes. Ann N Y Acad Sci 674:58-64
23. Dice JF, Walker CD, Byrne B, Cardiel A (1978) General characteristics of protein degradation in diabetes and starvation. Proc Natl Acad Sci USA 75:2093-2097
24. Dunn WAJ (1990a) Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J Cell Biol 110:1923-1933
25. Dunn WAJ (1990b) Studies on the mechanisms of autophagy: maturation of the autophagic vacuole. J Cell Biol 110:1935-1945
26. Ecker N, Mor A, Journo D, Abeliovich H (2010) Induction of autophagic flux by amino acid deprivation is distinct from nitrogen starvation-induced macroautophagy. Autophagy 6:879-890
27. Edinger AL, Thompson CB (2002) Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell 13:2276-2288
28. Edinger AL, Cinalli RM, Thompson CB (2003) Rab7 prevents growth factor-independent survival by inhibiting cell-autonomous nutrient transporter expression. Dev Cell 5:571-582
29. Fosse M, Berg TO, O'Reilly DS, Seglen PO (1995) Vanadate inhibition of hepatocytic autophagy. Calcium-modulated and osmolality-modulated antagonism by asparagine. Eur J Biochem 230:17-24
30. 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
31. 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
32. Graef M, Nunnari J (2011) Mitochondria regulate autophagy by conserved signalling pathways. EMBO J 30:2101-2114
33. 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
34. Gutierrez A, Chiva R, Sancho M, Beltran G, Arroyo-Lopez FN, Guillamon JM (2012) Nitrogen requirements of commercial wine yeast strains during fermentation of a synthetic grape must. Food Microbiol 31:25-32
35. 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
36. 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
37. Hao S, Sharp JW, Ross-Inta CM, McDaniel BJ, Anthony TG, Wek RC, Cavener DR, McGrath BC, Rudell JB, Koehnle TJ, Gietzen DW (2005) Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex. Science 307:1776-1778
38. Harding TM, Morano KA, Scott SV, Klionsky DJ (1995) Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol 131:591-602
39. Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell 6:1099-1108
40. Heitman J, Movva NR, Hall MN (1991) Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253:905-909
41. Hinnebusch AG (2005) Translational regulation of GCN4 and the general amino acid control of yeast. Annu Rev Microbiol 59:407-450
42. Holen I, Gordon PB, Stromhaug PE, Seglen PO (1996) Role of cAMP in the regulation of hepatocytic autophagy. Eur J Biochem 236:163-170
43. Horst M, Knecht EC, Schu PV (1999) Import into and degradation of cytosolic proteins by isolated yeast vacuoles. Mol Biol Cell 10:2879-2889
44. Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, Guan JL, Oshiro N, Mizushima N (2009) Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 20:1981-1991
45. Hughes AL, Gottschling DE (2012) An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast. Nature 492:261-265
46. Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, Ohsumi Y (2000) A ubiquitin-like system mediates protein lipidation. Nature 408:488-492
47. 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
48. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, Hall MN (2004) Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6:1122-1128
49. Juhasz G, Hill JH, Yan Y, Sass M, Baehrecke EH, Backer JM, Neufeld TP (2008) The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J Cell Biol 181:655-666
50. Kabeya Y, Kamada Y, Baba M, Takikawa H, Sasaki M, Ohsumi Y (2005) Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol Biol Cell 16:2544-2553
51. Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150:1507-1513
52. Kaufmann A, Beier V, Franquelim HG, Wollert T (2014) Molecular mechanism of autophagic membrane-scaffold assembly and disassembly. Cell 156:469-481
53. Kiffin R, Kaushik S, Zeng M, Bandyopadhyay U, Zhang C, Massey AC, Martinez-Vicente M, Cuervo AM (2007) Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age. J Cell Sci 120:782-791
54. Kihara A, Noda T, Ishihara N, Ohsumi Y (2001) Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol 152:519-530
55. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2002) mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110:163-175
56. Kim J, Kundu M, Viollet B, Guan KL (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13:132-141
57. 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
58. Klionsky DJ, Cueva R, Yaver DS (1992) Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway. J Cell Biol 119:287-299
59. Kon M, Kiffin R, Koga H, Chapochnick J, Macian F, Varticovski L, Cuervo AM (2011) Chaperone-mediated autophagy is required for tumor growth. Sci Transl Med 3:109ra117
60. Kraft C, Kijanska M, Kalie E, Siergiejuk E, Lee SS, Semplicio G, Stoffel I, Brezovich A, Verma M, Hansmann I, Ammerer G, Hofmann K, Tooze S, Peter M (2012) Binding of the Atg1/ULK1 kinase to the ubiquitin-like protein Atg8 regulates autophagy. EMBO J 31:3691-3703
61. Kuma A, Mizushima N, Ishihara N, Ohsumi Y (2002) Formation of the approximately 350-kDa Apg12-Apg5. Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J Biol Chem 277:18619-18625
62. Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T, Mizushima N (2004) The role of autophagy during the early neonatal starvation period. Nature 432:1032-1036
63. Kunz J, Henriquez R, Schneider U, Deuter-Reinhard M, Movva NR, Hall MN (1993) Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73:585-596
64. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672-676
65. Liu H, Wang P, Song W, Sun X (2009) Degradation of regulator of calcineurin 1 (RCAN1) is mediated by both chaperone-mediated autophagy and ubiquitin proteasome pathways. FASEB J 23:3383-3392
66. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P, Hall MN (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10:457-468
67. Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, Thompson CB (2005) Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120:237-248
68. Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, Zha Z, Liu Y, Li Z, Xu Y, Wang G, Huang Y, Xiong Y, Guan KL, Lei QY (2011) Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell 42:719-730
69. Mak SK, McCormack AL, Manning-Bog AB, Cuervo AM, Di Monte DA (2010) Lysosomal degradation of alpha-synuclein in vivo. J Biol Chem 285:13621-13629
70. Martinez-Vicente M, Talloczy Z, Kaushik S, Massey AC, Mazzulli J, Mosharov EV, Hodara R, Fredenburg R, Wu DC, Follenzi A, Dauer W, Przedborski S, Ischiropoulos H, Lansbury PT, Sulzer D, Cuervo AM (2008) Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest 118:777-788
71. Massey AC, Kaushik S, Sovak G, Kiffin R, Cuervo AM (2006) Consequences of the selective blockage of chaperone-mediated autophagy. Proc Natl Acad Sci USA 103:5805-5810
72. Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T (2009) Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol 11:385-396
73. Matsunaga K, Morita E, Saitoh T, Akira S, Ktistakis NT, Izumi T, Noda T, Yoshimori T (2010) Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. J Cell Biol 190:511-521
74. Matsuura A, Tsukada M, Wada Y, Ohsumi Y (1997) Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192:245-250
75. Maurin AC, Jousse C, Averous J, Parry L, Bruhat A, Cherasse Y, Zeng H, Zhang Y, Harding HP, Ron D, Fafournoux P (2005) The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores. Cell Metab 1:273-277
76. Maurin AC, Benani A, Lorsignol A, Brenachot X, Parry L, Carraro V, Guissard C, Averous J, Jousse C, Bruhat A, Chaveroux C, B'chir W, Muranishi Y, Ron D, Penicaud L, Fafournoux P (2014) Hypothalamic eIF2alpha signaling regulates food intake. Cell Rep 6:438-444
77. Merico A, Sulo P, Piskur J, Compagno C (2007) Fermentative lifestyle in yeasts belonging to the Saccharomyces complex. FEBS J 274:976-989
78. Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, George MD, Klionsky DJ, Ohsumi M, Ohsumi Y (1998) A protein conjugation system essential for autophagy. Nature 395:395-398
79. Mizushima N, Yamamoto A, Hatano M, Kobayashi Y, Kabeya Y, Suzuki K, Tokuhisa T, Ohsumi Y, Yoshimori T (2001) Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J Cell Biol 152:657-668
80. Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, Natsume T, Ohsumi Y, Yoshimori T (2003) Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J Cell Sci 116:1679-1688
81. Mortimore GE, Poso AR (1987) Intracellular protein catabolism and its control during nutrient deprivation and supply. Annu Rev Nutr 7:539-564
82. Nair U, Jotwani A, Geng J, Gammoh N, Richerson D, Yen WL, Griffith J, Nag S, Wang K, Moss T, Baba M, McNew JA, Jiang X, Reggiori F, Melia TJ, Klionsky DJ (2011) SNARE proteins are required for macroautophagy. Cell 146:290-302
83. 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
84. Nakatogawa H, Ohbayashi S, Sakoh-Nakatogawa M, Kakuta S, Suzuki SW, Kirisako H, Kondo-Kakuta C, Noda NN, Yamamoto H, Ohsumi Y (2012) The autophagy-related protein kinase Atg1 interacts with the ubiquitin-like protein Atg8 via the Atg8 family interacting motif to facilitate autophagosome formation. J Biol Chem 287:28503-28507
85. Noda T, Ohsumi Y (1998) Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273:3963-3966
86. Noda NN, Fujioka Y, Hanada T, Ohsumi Y, Inagaki F (2013) Structure of the Atg12-Atg5 conjugate reveals a platform for stimulating Atg8-PE conjugation. EMBO Rep 14:206-211
87. Odorizzi G, Babst M, Emr SD (2000) Phosphoinositide signaling and the regulation of membrane trafficking in yeast. Trends Biochem Sci 25:229-235
88. Ohashi Y, Munro S (2010) Membrane delivery to the yeast autophagosome from the Golgi-endosomal system. Mol Biol Cell 21:3998-4008
89. Orenstein SJ, Kuo SH, Tasset I, Arias E, Koga H, Fernandez-Carasa I, Cortes E, Honig LS, Dauer W, Consiglio A, Raya A, Sulzer D, Cuervo AM (2013) Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci 16:394-406
90. Papinski D, Schuschnig M, Reiter W, Wilhelm L, Barnes CA, Maiolica A, Hansmann I, Pfaffenwimmer T, Kijanska M, Stoffel I, Lee SS, Brezovich A, Lou JH, Turk BE, Aebersold R, Ammerer G, Peter M, Kraft C (2014) Early steps in autophagy depend on direct phosphorylation of atg9 by the atg1 kinase. Mol Cell 53:471-483
91. Ragusa MJ, Stanley RE, Hurley JH (2012) Architecture of the Atg17 complex as a scaffold for autophagosome biogenesis. Cell 151:1501-1512
92. Ravikumar B, Stewart A, Kita H, Kato K, Duden R, Rubinsztein DC (2003) Raised intracellular glucose concentrations reduce aggregation and cell death caused by mutant huntingtin exon 1 by decreasing mTOR phosphorylation and inducing autophagy. Hum Mol Genet 12:985-994
93. 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
94. Reggiori F, Wang CW, Nair U, Shintani T, Abeliovich H, Klionsky DJ (2004) Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae. Mol Biol Cell 15:2189-2204
95. 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
96. 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
97. Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM (2008) The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320:1496-1501
98. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM (2010) Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141:290-303
99. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14:1296-1302
100. Saucedo LJ, Gao X, Chiarelli DA, Li L, Pan D, Edgar BA (2003) Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol 5:566-571
101. Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26:1749-1760
102. Schmidt A, Beck T, Koller A, Kunz J, Hall MN (1998) The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. EMBO J 17:6924-6931
103. Scott SV, Nice DC, Nau JJ, Weisman LS, Kamada Y, Keizer-Gunnink I, Funakoshi T, Veenhuis M, Ohsumi Y, Klionsky DJ (2000) Apg13p and Vac8p are part of a complex of phosphoproteins that are required for cytoplasm to vacuole targeting. J Biol Chem 275:25840-25849
104. Seglen PO, Gordon PB, Holen I, Hoyvik H (1991) Hepatocytic autophagy. Biomed Biochim Acta 50:373-381
105. Shokat K, Velleca M (2002) Novel chemical genetic approaches to the discovery of signal transduction inhibitors. Drug Discov Today 7:872-879
106. Simonsen A, Wurmser AE, Emr SD, Stenmark H (2001) The role of phosphoinositides in membrane transport. Curr Opin Cell Biol 13:485-492
107. Smith EM, Finn SG, Tee AR, Browne GJ, Proud CG (2005) The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses. J Biol Chem 280:18717-18727
108. Suzuki SW, Onodera J, Ohsumi Y (2011) Starvation induced cell death in autophagy-defective yeast mutants is caused by mitochondria dysfunction. PLoS One 6:e17412
109. Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y (1992) Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 119:301-311
110. Talloczy Z, Jiang W, Virgin HW, Leib DA, Scheuner D, Kaufman RJ, Eskelinen EL, Levine B (2002) Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc Natl Acad Sci USA 99:190-195
111. Thumm M, Egner R, Koch B, Schlumpberger M, Straub M, Veenhuis M, Wolf DH (1994) Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett 349:275-280
112. Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169-174
113. Tsukamoto S, Kuma A, Murakami M, Kishi C, Yamamoto A, Mizushima N (2008) Autophagy is essential for preimplantation development of mouse embryos. Science 321:117-120
114. Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L (2008) Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J Biol Chem 283:23542-23556
115. Wang Y, Martinez-Vicente M, Kruger U, Kaushik S, Wong E, Mandelkow EM, Cuervo AM, Mandelkow E (2009) Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Hum Mol Genet 18:4153-4170
116. Weidberg H, Shpilka T, Shvets E, Abada A, Shimron F, Elazar Z (2011) LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev Cell 20:444-454
117. Weisman R, Roitburg I, Schonbrun M, Harari R, Kupiec M (2007) Opposite effects of tor1 and tor2 on nitrogen starvation responses in fission yeast. Genetics 175:1153-1162
118. Xie Z, Nair U, Klionsky DJ (2008) Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell 19:3290-3298
119. Yang Z, Klionsky DJ (2007) Permeases recycle amino acids resulting from autophagy. Autophagy 3:149-150
120. Yang Z, Huang J, Geng J, Nair U, Klionsky DJ (2006) Atg22 recycles amino acids to link the degradative and recycling functions of autophagy. Mol Biol Cell 17:5094-5104
121. Young AR, Chan EY, Hu XW, Kochl R, Crawshaw SG, High S, Hailey DW, Lippincott-Schwartz J, Tooze SA (2006) Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci 119:3888-3900
122. Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (2003) Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol 5:578-581