Protein turnover via autophagy: Implications for metabolism

Annual Review of Nutrition

Volumn 27, Issue , 2007, Pages 19-40

  Mizushima, Noboru ^a,b   Klionsky, Daniel J ^c  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^c UNIVERSITY OF MICHIGAN   (United States)

Author keywords

Amino acids; Neurodegeneration; Protein degradation; Proteolysis; Starvation

Indexed keywords

AMINO ACID; PROTEASOME;

AUTOPHAGY; CELL ACTIVITY; CYTOSOL; EUKARYOTE; HOMEOSTASIS; HUMAN; LYSOSOME; NEOPLASM; NERVE CELL; NERVE DEGENERATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN METABOLISM; REVIEW; STARVATION; CYTOPLASM; METABOLISM; PHYSIOLOGY; PROTEIN TRANSPORT; TRANSPORT AT THE CELLULAR LEVEL;

EUKARYOTA;

AMINO ACIDS; AUTOPHAGY; BIOLOGICAL TRANSPORT; CYTOPLASM; HUMANS; PROTEIN TRANSPORT;

EID: 34250864795     PISSN: 01999885     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.nutr.27.061406.093749     Document Type: Review

References (129)

1. Abeliovich H. 2004. Regulation of autophagy by the target of rapamycin. In Autophagy, ed. DJ Klionsky, pp. 60-69. Georgetown, TX: Landes Biosci.
2. Adhami F, Liao G, Morozov YM, Schloemer A, Schmithorst VJ, et al. 2006. Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy. Am. J. Pathol. 169:566-83
3. Adhami F, Schloemer A, Kuan CY. 2007. The roles of autophagy in cerebral ischemia. Autophagy 3:42-44
4. Ahlberg J, Berkenstam A, Henell F, Glaumann H. 1985. Degradation of short- and long-lived proteins in isolated rat liver lysosomes. Effects of pH, temperature, and proteolytic inhibitors. J. Biol. Chem. 260:5847-54
5. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. 2004. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431:805-10
6. Bassnett S. 2002. Lens organelle degradation. Exp. Eye Res. 74:1-6
7. Bellu AR, Komori M, van der Klei IJ, Kiel JAKW, Veenhuis M. 2001. Peroxisome biogenesis and selective degradation converge at Pex14p. J. Biol. Chem. 276:44570-74
8. Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, et al. 2005. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J. Cell Biol. 171:603-14
9. Cahill GF Jr. 1970. Starvation in man. N. Engl. J. Med. 282:668-75
10. Chikenji T, Elwyn DH, Kinney JM. 1983. Protein synthesis rates in rat muscle and skin based on Lysyl-tRNA radioactivity. J. Surg. Res. 34:68-82
11. Cuervo AM, Bergamini E, Brunk UT, Droge W, Ffrench M, Terman A. 2005. Autophagy and aging: the importance of maintaining "clean" cells. Autophagy 1:131-40
12. Debnath J, Baehrecke EH, Kroemer G. 2005. Does autophagy contribute to cell death? Autophagy 1:66-74
13. Doherty FJ, Osborn NU, Wassell JA, Heggie PE, Laszlo L, Mayer RJ. 1989. Ubiquitin-protein conjugates accumulate in the lysosomal system of fibroblasts treated with cysteine proteinase inhibitors. Biochem. J. 263:47-55
14. Dunn WA Jr. 1990. Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J. Cell Biol. 110:1923-33
15. Dunn WA Jr, Cregg JM, Kiel JAKW, van der Klei IJ, Oku M, et al. 2005. Pexophagy: the selective autophagy of peroxisomes. Autophagy 1:75-83
16. Fuertes G, Martin De Llano JJ, Villarroya A, Rivett AJ, Knecht E. 2003. Changes in the proteolytic activities of proteasomes and lysosomes in human fibroblasts produced by serum withdrawal, amino-acid deprivation and confluent conditions. Biochem. J. 375:75-86
17. Hamasaki M, Noda T, Baba M, Ohsumi Y. 2005. Starvation triggers the delivery of the endoplasmic reticulum to the vacuole via autophagy in yeast. Traffic 6:56-65
18. Hamasaki M, Noda T, Ohsumi Y. 2003. The early secretory pathway contributes to autophagy in yeast. Cell Struct. Funct. 28:49-54
19. Hanada T, Ohsumi Y. 2005. Structure-function relationship of Atg12, a ubiquitin-like modifier essential for autophagy. Autophagy 1:110-18
20. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, et al. 2006. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885-89
21. Harris RA, Goodwin GW, Paxton R, Dexter P, Powell SM, et al. 1989. Nutritional and hormonal regulation of the activity state of hepatic branched-chain alpha-keto acid dehydrogenase complex. Ann. NY Acad. Sci. 573:306-13
22. Hemelaar J, Lelyveld VS, Kessler BM, Ploegh HL. 2003. A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP and Apg8L. J. Biol. Chem. 278:51841-50
23. Huang W-P, Scott SV, Kim J, Klionsky DJ. 2000. The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. J. Biol. Chem. 275:5845-51
24. Hutchins MU, Veenhuis M, Klionsky DJ. 1999. Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway. J. Cell Sci. 112:4079-87
25. Hutson NJ, Mortimore GE. 1982. Suppression of cytoplasmic protein uptake by lysosomes as the mechanism of protein regain in livers of starved-refed mice. J. Biol. Chem. 257:9548-54
26. Ichimura Y, Imamura Y, Emoto K, Umeda M, Noda T, Ohsumi Y. 2004. In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy. J. Biol. Chem. 279:40584-92
27. Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, et al. 2000. A ubiquitin-like system mediates protein lipidation. Nature 408:488-92
28. Ishihara N, Hamasaki M, Yokota S, Suzuki K, Kamada Y, et al. 2001. Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol. Biol. Cell 12:3690-702
29. Ishii T, Yanagawa T, Kawane T, Yuki K, Seita J, et al. 1996. Murine peritoneal macrophages induce a novel 60-kDa protein with structural similarity to a tyrosine kinase p56lck-associated protein in response to oxidative stress. Biochem. Biophys. Res. Commun. 226:456-60
30. Iwata J, Ezaki J, Komatsu M, Yokota S, Ueno T, et al. 2006. Excess peroxisomes are degraded by autophagic machinery in mammals. J. Biol. Chem. 281:4035-41
31. Joung I, Strominger JL, Shin J. 1996. Molecular cloning of a phosphotyrosine-independent ligand of the p561ck SH2 domain. Proc. Natl. Acad. Sci. USA 93:5991-95
32. Juhasz G, Csikos G, Sinka R, Erdelyi M, Sass M. 2003. The Drosophila homolog of Aut1 is essential for autophagy and development. FEBS Lett. 543:154-58
33. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, et al. 2000. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19:5720-28
34. Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T. 2004. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J. Cell Sci. 117:2805-12
35. Kadowaki M, Kanazawa T. 2003. Amino acids as regulators of proteolysis. J. Nutr. 133:2052-56S
36. Kamada Y, Sekito T, Ohsumi Y. 2004. Autophagy in yeast: a TOR-mediated response to nutrient starvation. Curr. Top. Microbiol. Immunol. 279:73-84
37. Kato H, Takahashi S, Takenaka A, Funabiki R, Noguchi T, Naito H. 1989. Degradation of endogenous proteins and internalized asialofetuin in primary cultured hepatocytes of rats. Int. J. Biochem. 21:483-95
38. Kawamata T, Kamada Y, Suzuki K, Kuboshima N, Akimatsu H, et al. 2005. Characterization of a novel autophagy-specific gene, ATG29. Biochem. Biophys. Res. Commun. 338:1884-89
39. Kim J, Dalton VM, Eggerton KP, Scott SV, Klionsky DJ. 1999. Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways. Mol. Biol. Cell 10:1337-51
40. Kim J, Klionsky DJ. 2000. Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and mammalian cells. Annu. Rev. Biochem. 69:303-42
41. Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, et al. 1999. Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J. Cell Biol. 147:435-46
42. Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, et al. 2000. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J. Cell Biol. 151:263-76
43. Kirkegaard K, Taylor MP, Jackson WT. 2004. Cellular autophagy: surrender, avoidance and subversion by microorganisms. Nat. Rev. Microbiol. 2:301-14
44. Kissova I, Deffieu M, Manon S, Camougrand N. 2004. Uth1p is involved in the autophagic degradation of mitochondria. J. Biol. Chem. 279:39068-74
45. Klionsky DJ. 2005. The molecular machinery of autophagy: unanswered questions. J. Cell Sci. 118:7-18
46. Klionsky DJ, Cregg JM, Dunn WAJ, Emr SD, Sakai Y, et al. 2003.Aunifiednomenclature for yeast autophagy-related genes. Dev. Cell 5:539-45
47. Klionsky DJ, Cuervo AM, Seglen PO. 2007. Methods for monitoring autophagy from yeast to human. Autophagy 3:In press
48. Klionsky DJ, Meijer AJ, Codogno P, Neufeld TP, Scott RC. 2005. Autophagy and p70S6 kinase. Autophagy 1:59-61
49. Klionsky DJ, Ohsumi Y. 1999. Vacuolar import of proteins and organelles from the cytoplasm. Annu. Rev. Cell Dev. Biol. 15:1-32
50. Köchl R, Hu XW, Chan EYW, Tooze SA. 2006. Microtubules facilitate autophagosome formation and fusion of autophagosomes with endosomes. Traffic 7:129-45
51. Koike M, Shibata M, Waguri S, Yoshimura K, Tanida I, et al. 2005. Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroidlipofuscinoses (Batten disease). Am. J. Pathol. 167:1713-28
52. Komatsu M, Waguri S, Chiba T, Murata S, Iwata JI, et al. 2006. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880-84
53. Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, et al. 2005. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169:425-34
54. Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, et al. 2004. The role of autophagy during the early neonatal starvation period. Nature 432:1032-36
55. 54a. Kuma A, Matsui M, Mizushima N. 2007. LC3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of LC3 localization. Autophagy 3: In press
56. 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. 277:18619-25
57. Laszlo L, Doherty FJ, Osborn NU, Mayer RJ. 1990. Ubiquitinated protein conjugates are specifically enriched in the lysosomal system of fibroblasts. FEBS Lett. 261:365-68
58. Laurin N, Brown JP, Morissette J, Raymond V. 2002. Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am. J. Hum. Genet. 70:1582-88
59. Lenk SE, Susan PP, Hickson I, Jasionowski T, Dunn WA Jr. 1999. Ubiquitinated aldolase B accumulates during starvation-induced lysosomal proteolysis. J. Cell Physiol. 178:17-27
60. Levine B, Klionsky DJ. 2004. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6:463-77
61. Lum JJ, Bauer DE, Kong M, Harris MH, Li C, et al. 2005. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120:237-48
62. Marino G, Uria JA, Puente XS, Quesada V, Bordallo J, Lopez-Otin C. 2003. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J. Biol. Chem. 278:3671-78
63. 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 103:5805-10
64. Massey AC, Zhang C, Cuervo AM. 2006. Chaperone-mediated autophagy in aging and disease. Curr. Top. Dev. Biol. 73:205-35
65. Matsui M, Yamamoto A, Kuma A, Ohsumi Y, Mizushima N. 2006. Organelle degradation during the lens and erythroid differentiation is independent of autophagy. Biochem. Biophys. Res. Commun. 339:485-89
66. Meijer AJ, Codogno P. 2004. Regulation and role of autophagy in mammalian cells. Int. J. Biochem. Cell Biol. 36:2445-62
67. Melendez A, Talloczy Z, Seaman M, Eskelinen E-L, Hall DH, Levine B. 2003. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301:1387-91
68. Mizushima N. 2004. Methods for monitoring autophagy. Int. J. Biochem. Cell Biol. 36:2491-502
69. Mizushima N. 2005. The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ. 12:1535-41
70. Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, et al. 2003. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J. Cell Sci. 116:1679-88
71. Mizushima N, Noda T, Ohsumi Y. 1999. Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. EMBO J. 18:3888-96
72. Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, et al. 1998. A protein conjugation system essential for autophagy. Nature 395:395-98
73. Mizushima N, Sugita H, Yoshimori T, Ohsumi Y. 1998. A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J. Biol. Chem. 273:33889-92
74. Mizushima N, Yamamoto A, Hatano M, Kobayashi Y, Kabeya Y, et al. 2001. Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J. Cell Biol. 152:657-67
75. Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. 2004. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15:1101-11
76. Mizushima N, Yoshimori T, Ohsumi Y. 2002. Mouse Apg10 as an Apg 12-conjugating enzyme: analysis by the conjugation-mediated yeast two-hybrid method. FEBS Lett. 532:450-54
77. Moller MTN, Samari HR, Holden L, Seglen PO. 2004. Regulation of mammalian autophagy by protein phosphorylation. In Autophagy, ed. DJ Klionsky, pp. 48-59. Georgetown, TX: Landes Biosci.
78. Moriwaki H, Miwa Y, Tajika M, Kato M, Fukushima H, Shiraki M. 2004. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem. Biophys. Res. Commun. 313:405-9
79. Mortimore GE, Poso AR. 1987. Intracellular protein catabolism and its control during nutrient deprivation and supply. Annu. Rev. Nutr. 7:539-64
80. Munz C. 2006. Autophagy and antigen presentation. Cell Microbiol. 8:891-98
81. Nair U, Klionsky DJ. 2005. Molecular mechanisms and regulation of specific and non-specific autophagy pathways in yeast. J. Biol. Chem. 280:41785-88
82. Nakagawa I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H, et al. 2004. Autophagy defends cells against invading group A Streptococcus. Science 306:1037-40
83. Nemoto T, Tanida I, Tanida-Miyake E, Minematsu-Ikeguchi N, Yokota M, et al. 2003. The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, facilitates MAP-LC3 modification. J. Biol. Chem. 278:39517-26
84. Nishimoto S, Kawane K, Watanabe-Fukunaga R, Fukuyama H, Ohsawa Y, et al. 2003. Nuclear cataract caused by a lack of DNA degradation in the mouse eye lens. Nature 424:1071-74
85. Ogawa M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, Sasakawa C. 2005. Escape of intracellular Shigella from autophagy. Science 307:727-31
86. Ohsumi Y. 2001. Molecular dissection of autophagy: two ubiquitin-like systems. Nat. Rev. Mol. Cell Biol. 2:211-16
87. Ohsumi Y, Mizushima N. 2004. Two ubiquitin-like conjugation systems essential for autophagy. Semin. Cell Dev. Biol. 15:231-36
88. Onodera J, Ohsumi Y. 2004. Ald6p is a preferred target for autophagy in yeast, Saccharomyces cerevisiae. J. Biol. Chem. 279:16071-76
89. Onodera J, Ohsumi Y. 2005. Autophagy is required for maintenance of amino acid levels and protein synthesis under nitrogen starvation. J. Biol. Chem. 280:31582-86
90. Otto GP, Wu MY, Kazgan N, Anderson OR, Kessin RH. 2003. Macroautophagy is required for multicellular development of the social amoeba Dictyostelium discoideum. J. Biol. Chem. 278:17636-45
91. Palou A, Remesar X, Arola L, Herrera E, Alemany M. 1981. Metabolic effects of short-term food deprivation in the rat. Horm. Metab. Res. 13:326-30
92. Pfeifer U. 1978. Inhibition by insulin of the formation of autophagic vacuoles in rat liver. A morphometric approach to the kinetics of intracellular degradation by autophagy. J. Cell Biol. 78:152-67
93. Puls A, Schmidt S, Grawe F, Stabel S. 1997. Interaction of protein kinase Cζ, with ZIP, a novel protein kinase C-binding protein. Proc. Natl. Acad. Sci. USA 94:6191-96
94. Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, et al. 2003. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 112:1809-20
95. Reggiori F, Shintani T, Nair U, Klionsky DJ. 2005. Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts. Autophagy 1:101-9
96. Reggiori F, Wang C-W, 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 15:2189-204
97. Rodriguez A, Duran A, Selloum M, Champy MF, Diez-Guerra FJ, et al. 2006. Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62. Cell Metab. 3:211-22
98. Rodriguez-Enriquez S, Kim I, Currin RT, Lemasters JJ. 2006. Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy 2:39-46
99. Rubinsztein DC, Difiglia M, Heintz N, Nixon RA, Qin ZH, et al. 2005. Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy 1:11-22
100. Sagiv Y, Legesse-Miller A, Porat A, Elazar Z. 2000. GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28. EMBO J. 19:1494-504
101. Sanz L, Diaz-Meco MT, Nakano H, Moscat J. 2000. The atypical PKC-interacting protein p62 channels NF-κB activation by the IL-1-TRAF6 pathway. EMBO J. 19:1576-86
102. Schwartz AL, Ciechanover A, Brandt RA, Geuze HJ. 1988. Immunoelectron microscopic localization of ubiquitin in hepatoma cells. EMBO J. 7:2961-66
103. Schworer CM, Shiffer KA, Mortimore GE. 1981. Quantitative relationship between autophagy and proteolysis during graded amino acid deprivation in perfused rat liver. J. Biol. Chem. 256:7652-58
104. Scott RC, Schuldiner O, Neufeld TP. 2004. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev. Cell 7:167-78
105. Seglen PO, Gordon PB. 1981. Vanadate inhibits protein degradation in isolated rat hepatocytes. J. Biol. Chem. 256:7699-701
106. Shenoy ST, Rogers QR. 1977. Effect of starvation on the charging levels of transfer ribonucleic acid and total acceptor capacity in rat liver. Biochim. Biophys. Acta 476:218-27
107. Shintani T, Klionsky DJ. 2004. Autophagy in health and disease: a double-edged sword. Science 306:990-95
108. Shintani T, Mizushima N, Ogawa Y, Matsuura A, Noda T, Ohsumi Y. 1999. Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast. EMBO J. 18:5234-41
109. Stasyk OV, Stasyk OG, Mathewson RD, Farre JC, Nazarko VY, et al. 2006. Atg28, a novel coiled-coil protein involved in autophagic degradation of peroxisomes in the methylotrophic yeast Pichia pastoris. Autophagy 2:30-38
110. Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F. 2003. Crystallization and preliminary X-ray analysis of LC3-I. Acta Crystallogr. D Biol. Crystallogr. 59:1464-65
111. Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F. 2004. The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8. Genes Cells 9:611-18
112. Suzuki K, Kirisako T, Kamada Y, Mizushima N, Noda T, Ohsumi Y. 2001. The preautophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J. 20:5971-81
113. Suzuki NN, Yoshimoto K, Fujioka Y, Ohsumi Y, Inagaki F. 2005. The crystal structure of plant ATG12 and its biological implication in autophagy. Autophagy 1:119-26
114. 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. 119:301-11
115. Tanida I, Minematsu-Ikeguchi N, Ueno T, Kominami E. 2005. Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy 1:84-91
116. Tanida I, Mizushima N, Kiyooka M, Ohsumi M, Ueno T, et al. 1999. Apg7p/Cvt2p: a novel protein-activating enzyme essential for autophagy. Mol. Biol. Cell 10:1367-79
117. Tanida I, Tanida-Miyake E, Ueno T, Kominami E. 2001. The human homolog of Saccharomyces cerevisiae Apg7p is a protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3. J. Biol. Chem. 276:1701-6
118. Tsukada M, Ohsumi Y. 1993. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 333:169-74
119. Ueno T, Kominami E. 1991. Mechanism and regulation of lysosomal sequestration and proteolysis. Biomed. Biochim. Acta 50:365-71
120. Vabulas RM, Hard FU. 2005. Protein synthesis upon acute nutrient restriction relies on proteasome function. Science 310:1960-63
121. Wang C-W, Klionsky DJ. 2003. The molecular mechanism of autophagy. Mol. Med. 9:65-76
122. A receptors and the cytoskeleton. Nature 397:69-72
123. Wang QJ, Ding Y, Kohtz S, Mizushima N, Cristea IM, et al. 2006. Induction of autophagy in axonal dystrophy and degeneration. J. Neurosci. 26:8057-68
124. 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. 17:5094-104
125. Yorimitsu T, Klionsky DJ. 2005. Autophagy: molecular machinery for self-eating. Cell Death Differ. 12(Suppl. 2):1542-52
126. Young VR, Scrimshaw NS. 1971. The physiology of starvation. Sci. Am. 225:14-21
127. Yu WH, Cuervo AM, Kumar A, Peterhoff CM, Schmidt SD, et al. 2005. Macroautophagy - a novel β-amyloid (Aβ) peptide-generating pathway activated in Alzheimer's disease. J. Cell Biol. 171:87-98
128. Yuan W, Stromhaug PE, Dunn WA Jr. 1999. Glucose-induced autophagy of peroxisomes in Pichiapastoris requires a unique E1-like protein. Mol. Biol. Cell 10:1353-66
129. Yue Z, Jin S, Yang C, Levine AJ, Heintz N. 2003. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. USA 100:15077-82