Autophagy in the Pathogenesis of Disease

Cell

Volumn 132, Issue 1, 2008, Pages 27-42

  Levine, Beth ^a   Kroemer, Guido ^b,c,d  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b INSTITUT GUSTAVE ROUSSY   (France)

^c UNIVERSITÉ PARIS SACLAY   (France)

^d INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

LITHIUM CHLORIDE; RAPAMYCIN DERIVATIVE;

AGING; ALZHEIMER DISEASE; AUTOPHAGY; CELL DEATH; CELL ORGANELLE; CELL SURVIVAL; DANON DISEASE; DEGENERATIVE DISEASE; ENERGY; GENOME; HEART DISEASE; HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; IMMUNITY; INFECTION; INFLAMMATORY DISEASE; LIVER DISEASE; LYSOSOME; METABOLIC STRESS; MUSCLE DISEASE; NEOPLASM; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRION DISEASE; PRIORITY JOURNAL; REVIEW;

AGING; ANIMALS; AUTOPHAGY; CELL DEATH; CELL SURVIVAL; DISEASE; GENOMIC INSTABILITY; HOMEOSTASIS; HUMANS; LYSOSOMES; OXIDATIVE STRESS;

EID: 37649005234     PISSN: 00928674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cell.2007.12.018     Document Type: Review

References (101)

1. Amaravadi R.K., Yu D., Lum J.J., Bui T., Christophorou M.A., Evan G.I., Thomas-Tikhonenko A., and Thompson C.B. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J. Clin. Invest. 117 (2007) 326-336
2. Apetoh L., Ghriringhelli F., Tesniere A., Obeid M., Ortiz C., Criollo A., Mignot G., Maiuri M.C., Ullrich E., Saulnier P., et al. Toll-like receptor 4-dependent contribution of the immune system to anti-cancer chemotherapy and radiotherapy. Nat. Med. 13 (2007) 1050-1059
3. Askanas V., and Engel W.K. Inclusion-body myositis: a myodegenerative conformational disorder associated with Aβ, protein misfolding, and proteasome inhibition. Neurology 66 (2006) S39-S48
4. Bahro M., and Pfeifer U. Short-term stimulation by propanolol and verapamil of cardiac cellular autophagy. J. Mol. Cell. Cardiol. 19 (1987) 1169-1178
5. Bassham D.C., Laporte M., Marty F., Moriyasu Y., Ohsumi Y., Olsen L.J., and Yoshimoto K. Autophagy in development and stress responses of plants. Autophagy 2 (2006) 2-11
6. Baumgart D.C., and Carding S.R. Inflammatory bowel disease: cause and immunobiology. Lancet 369 (2007) 1627-1647
7. Bergamini E. Targets for antiageing drugs. Expert Opin. Ther. Targets 9 (2005) 77-82
8. Bolanos-Meade J., Zhou L., Hoke A., Corse A., Vogelsang G., and Wagner K.R. Hydroxychloroquine causes severe vacuolar myopathy in a patient with chronic graft-versus-host disease. Am. J. Hematol. 78 (2005) 306-309
9. Cao Y., Espinola J.A., Fossale E., Massey A.C., Cuervo A.M., MacDonald M.E., and Cotman S.L. Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis. J. Biol. Chem. 281 (2006) 20483-20493
10. Crighton D., Wilkinson S., O'Prey J., Syed N., Smith P., Harrison P.R., Gasco M., Garrone O., Crook T., and Ryan K.M. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 126 (2006) 121-134
11. Criollo A., Maiuri M.C., Tasdemir E., Vitale I., Fiebig A.A., Andrews D., Molgo J., Diaz J., Lavandero S., Harper F., et al. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 14 (2007) 1029-1039
12. Cully M., You H., Levine A.J., and Mak T.W. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat. Rev. Cancer 6 (2006) 184-192
13. de Duve C., and Wattiaux R. The lysosome. Annu. Rev. Physiol. 28 (1966) 435-492
14. Degenhardt K., Mathew R., Beaudoin B., Bray K., Anderson D., Chen G., Mukherjee C., Shi Y., Gelinas C., Fan Y., et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10 (2006) 51-64
15. Del Roso A., Vittorini S., Cavallini G., Donati A., Gori Z., Masini M., Pollera M., and Bergamini E. Ageing-related changes in the in vivo function of rat liver macroautophagy and proteolysis. Exp. Gerontol. 38 (2003) 519-527
16. Espert L., Denizot M., Grimaldi M., Robert-Hebmann V., Gay B., Varbanov M., Codogno P., and Biard-Piechaczyk M. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J. Clin. Invest. 116 (2006) 2161-2172
17. Felbor U., Kessler B., Mothes W., Goebel H.H., Ploegh H.L., Bronson R.T., and Olsen B.R. Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc. Natl. Acad. Sci. USA 99 (2002) 7883-7888
18. Feng Z., Zhang H., Levine A.J., and Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl. Acad. Sci. USA 102 (2005) 8204-8209
19. Fimia G.M., Stoykova A., Romagnoli A., Giunta L., Di Bartolomeo S., Nardacci R., Corazzari M., Fuoco C., Ucar A., Schwartz P., et al. Ambra1 regulates autophagy and development of the nervous system. Nature 447 (2007) 1121-1125
20. Fukuda T., Ahearn M., Roberts A., Mattaliano R.J., Zaal K., Ralston E., Plotz P.H., and Raben N. Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease. Mol. Ther. 14 (2006) 831-839
21. Gozuacik D., and Kimchi A. DAPk protein family and cancer. Autophagy 2 (2006) 74-79
22. Grossmayer G.E., Munoz L.E., Gaipl U.S., Franz S., Sheriff A., Voll R.E., Kalden J.R., and Hermann M. Removal of dying cells and systemic lupus erythematous. Mod. Rheumatol. 15 (2005) 383-390
23. Guarente L., and Kenyon C. Genetic pathways that regulate ageing in model organisms. Nature 408 (2000) 255-262
24. Hamacher-Brady A., Brady N.R., and Gottlieb R.A. Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J. Biol. Chem. 281 (2006) 29776-29787
25. Hara T., Nakamura K., Matsui M., Yamamoto A., Nakahara Y., Suzuki-Migishima R., Yokoyama M., Mishima K., Saito I., Okano H., and Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441 (2006) 885-889
26. Iwata J., Ezaki J., Komatsu M., Yokota S., Ueno T., Tanida I., Chiba T., Tanaka K., and Kominami E. Excess peroxisomes are degraded by autophagic machinery in mammals. J. Biol. Chem. 281 (2006) 4035-4041
27. Ji H., Ramsey M.R., Hayes D.N., Fan C., McNamara K., Kozlowski P., Torrice C., Wu M.C., Shimamura T., Perea S.A., et al. LKB1 modulates lung cancer differentiation and metastastis. Nat. Rev. Cancer 448 (2007) 807-811
28. Jia K., and Levine B. Autophagy is required for dietary restriction-mediated lifespan extension in C. elegans. Autophagy 3 (2007) 597-599
29. Jia K., Hart A.C., and Levine B. Autophagy genes protect against disease caused by polyglutamine expansion proteins in Caenorhabditis elegans. Autophagy 3 (2007) 21-25
30. Jin S., and White E. Role of autophagy in cancer: management of metabolic stress. Autophagy 3 (2007) 28-31
31. Kamimoto T., Shoji S., Hidvegi T., Mizushima N., Umebayashi K., Perlmutter D.H., and Yoshimori T. Intracellular inclusions containing mutant α-1 antitrypsin Z are propagated in the absence of autophagic activity. J. Biol. Chem. 281 (2006) 4467-4476
32. Kang C., You Y.-J., and Avery L. Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. Genes Dev. 21 (2007) 2161-2171
33. Karantza-Wadsworth V., Patel S., Kravchuk O., Chen G., Mathew R., Jin S., and White E. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 21 (2007) 1621-1635
34. Kenyon C. The plasticity of aging: insights from long-lived mutants. Cell 120 (2005) 449-460
35. Kim I., Rodriquez-Enriquez S., and Lemasters J.J. Selective degradation of mitochondria by mitophagy. Arch. Biochem. Biophys. 462 (2007) 245-253
36. Klionsky D.J. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat. Rev. Mol. Cell Biol. 8 (2007) 931-937
37. Koneri K., Goi T., Hirono Y., Katayama K., and Yamaguchi A. Beclin 1 gene inhibits tumor growth in colon cancer cell lines. Anticancer Res. 27 (2007) 1453-1457
38. Koike M., Shibata M., Waguri S., Yoshimura K., Tanida I., Kominami E., Gotow T., Peters C., von Figura K., Mizushima N., et al. Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease). Am. J. Pathol. 167 (2005) 1713-1728
39. Komatsu M., Waguri S., Ueno T., Iwata J., Murata S., Tanida I., Ezaki J., Mizushima N., Ohsumi Y., Uchiyama Y., et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169 (2005) 425-434
40. Komatsu M., Waguri S., Chiba T., Murata S., Iwata J., Tanida I., Ueno T., Koike M., Uchiyama Y., Kominami E., and Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441 (2006) 880-884
41. Kuma A., Hatano M., Matsui M., Yamamoto A., Nakaya H., Yoshimori T., Ohsumi Y., Tokuhisa T., and Mizushima N. The role of autophagy during the early neonatal starvation period. Nature 432 (2004) 1032-1036
42. Lee H.K., Lund J.M., Ramanathan B., Mizushima N., and Iwasaki A. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315 (2007) 1398-1401
43. Levine B. Cell biology: autophagy and cancer. Nature 446 (2007) 745-747
44. Levine B., and Deretic V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat. Rev. Immunol. 7 (2007) 767-777
45. Levine B., and Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6 (2004) 463-477
46. Li C., Capan E., Zhao Y., Zhao J., Stolz D., Watkins S.C., Jin S., and Lu B. Autophagy is induced in CD4+ T cells and important for the growth-factor withdrawal cell death. J. Immunol. 177 (2006) 5163-5168
47. Liang C., Feng P., Ku B., Dotan I., Canaani D., Oh B.H., and Jung J.U. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat. Cell Biol. 8 (2006) 688-699
48. Liang J., Shao S.H., Xu Z.X., Hennessy B., Ding Z., Larrea M., Kondo S., Dumont D.J., Gutterman J.U., Walker C.L., et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat. Cell Biol. 9 (2007) 218-224
49. Liang X.H., Jackson S., Seaman M., Brown K., Kempkes B., Hibshoosh H., and Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402 (1999) 672-676
50. Lucas G.J., Daroscewska A., and Ralston S.H. Contribution of genetic factors to the pathogenesis of Paget's disease of bone and related disorders. J. Bone Miner. Res. 21 (2006) 31-37
51. Lum J.J., Bauer D.E., Kong M., Harris M.H., Li C., Lindsten T., and Thompson C.B. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120 (2005) 237-248
52. Lunemann J.D., Schmidt J., Schmid D., Barthel K., Wrede A., Dalakas M.C., and Munz C. β-Amyloid is a substrate of autophagy in sporadic inclusion body myositis. Ann. Neurol. 61 (2007) 476-483
53. Maiuri M.C., Zalckvar E., Kimchi A., and Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 8 (2007) 741-752
54. Maiuri M.C., Le Toumelin G., Criollo A., Rain J.C., Gautier F., Juin P., Tasdemir E., Pierron G., Troulinaki K., Tavernarakis N., et al. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J. 26 (2007) 2527-2539
55. Marino G., Salvador-Montoliu N., Fueyo A., Knecht E., Mizushima N., and Lopez-Otin C. Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. J. Biol. Chem. 282 (2007) 18573-18583
56. Martinez-Vicente M., and Cuervo A.M. Autophagy and neurodegeneration: when the cleaning crew goes on strike. Lancet Neurol. 6 (2007) 352-361
57. Massey D.C., and Parkes M. Genome-wide association scanning highlights two autophagy genes, ATG16L and IRGM, as being significantly associated with Crohn's disease. Autophagy 3 (2007) 649-651
58. Mathew R., Karantza-Wadsworth V., and White E. Role of autophagy in cancer. Nat. Rev. Cancer 7 (2007) 961-967
59. Mathew R., Kongara S., Beaudoin B., Karp C.M., Bray K., Degenhardt K., Chen G., Jin S., and White E. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 21 (2007) 1367-1381
60. Matsui Y., Takagi H., Qu X., Abdellatif M., Sakoda H., Asano T., Levine B., and Sadoshima J. Distinct roles of autophagy in the heart during ischemia and reperfusion. Circ. Res. 100 (2007) 914-922
61. Meijer A.J., and Codogno P. Signalling and autophagy regulation in health, aging, and disease. Mol. Aspects Med. 27 (2006) 411-425
62. Melendez A., Talloczy Z., Seaman M., Eskelinen E.L., Hall D.H., and Levine B. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301 (2003) 1387-1391
63. Miracco C., Cosci E., Oliveri G., Luzi P., Pacenti L., Monciatti I., Mannucci S., De Nisi M.C., Toscano M., Malagnino V., et al. Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumors. Int. J. Oncol. 30 (2007) 429-436
64. Mizushima N., and Klionsky D. Protein turnover via autophagy: implications for metabolism. Annu. Rev. Nutr. 27 (2007) 19-40
65. Mizushima N., Yamamoto A., Matsui M., Yoshimori T., and Ohsumi Y. In vivo analysis of autophagy in responose to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15 (2004) 1101-1111
66. Nair U., and Klionsky D.J. Molecular mechanisms and regulation of specific and nonspecific autophagy pathways in yeast. J. Biol. Chem. 280 (2005) 41785-41788
67. Nakagawa I., Amano A., Mizushima N., Yamamoto A., Yamaguchi H., Kamimoto T., Nara A., Funao J., Nakata M., Tsuda K., et al. Autophagy defends cells against invading group A Streptococcus. Science 306 (2004) 1037-1040
68. Nakai A., Yamaguchi O., Takeda T., Higuchi Y., Hikoso S., Taniike M., Omiya S., Mizote I., Matsumura Y., Asahi M., et al. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat. Med. 13 (2007) 619-624
69. Nishino I. Autophagic vacuolar myopathy. Semin. Pediatr. Neurol. 13 (2006) 90-95
70. Nishino I., Fu J., Tanji K., Yamada T., Shimojo S., Koori T., Mora M., Riggs J.E., Oh S.J., Koga Y., et al. Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 406 (2000) 906-910
71. Orvedahl A., Alexander D., Talloczy Z., Sun Q., Wei Y., Zhang W., Burns D., Leib D.A., and Levine B. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1 (2007) 23-35
72. Pandey U.B., Nie Z., Batlevi Y., McCray B.A., Ritson G.P., Nedelsky N.B., Schwartz S.L., DiProspero N.A., Knight M.A., Schuldiner O., et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447 (2007) 859-863
73. Pankiv S., Hoyvarade Clausen T., Lamark T., Brech A., Bruun J.A., Outzen H., Overvatn A., Bjorkoy G., and Johansen T. p62/SGSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 282 (2007) 24131-24135
74. Pattingre S., Tassa A., Qu X., Garuti R., Liang X.H., Mizushima N., Packer M., Schneider M.D., and Levine B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122 (2005) 927-939
75. Perlmutter D.H. The role of autophagy in alpha-1-antitrypsin deficiency. Autophagy 2 (2006) 258-263
76. Pinkston J.M., Garigan D., Hansen M., and Kenyon C. Mutations that increase the life span of C. elegans inhibit tumor growth. Science 313 (2006) 971-975
77. Pua H.H., Dzhagalov I., Chuck M., Mizushima N., and He Y.W. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J. Exp. Med. 204 (2007) 25-31
78. Puls I., Oh S.J., Summer C.J., Wallace K.E., Floeter M.K., Mann E.A., Kennedy W.R., Wendelschafer-Crabb G., Vortmeyer A., Powers R., et al. Distal spinal and bulbar muscular atrophy caused by dynactin mutation. Ann. Neurol. 57 (2005) 687-694
79. Qu X., Yu J., Bhagat G., Furuya N., Hibshoosh H., Troxel A., Rosen J., Eskelinen E.L., Mizushima N., Ohsumi Y., et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 112 (2003) 1809-1820
80. Qu X., Zou Z., Sun Q., Luby-Phelps K., Cheng P., Hogan R.N., Gilpin C., and Levine B. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128 (2007) 931-946
81. Ravikumar B., Acevedo-Arozena A., Imarisio S., Berger Z., Vacher C., O'Kane C.J., Brown S.D., and Rubinsztein D.C. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat. Genet. 37 (2005) 771-776
82. Rubinsztein D.C., Gestwicki J.E., Murphy L.O., and Klionsky D.J. Potential therapeutic applications of autophagy. Nat. Rev. Drug Discov. 6 (2007) 304-312
83. Sarkar S., Perlstein E.O., Imarisio S., Pineau S., Cordenier A., Maglathlin R.L., Webster J.A., Lewis T.A., O'Kane C.J., Schreiber S.L., and Rubinsztein D.C. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat. Chem. Biol. 3 (2007) 331-338
84. Schmid D., and Munz C. Innate and adaptive immunity through autophagy. Immunity 27 (2007) 11-21
85. Schwartz R.A., Fernandez G., Kotulska K., and Jozwiak S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J. Am. Acad. Dermatol. 57 (2007) 189-202
86. Scott R.C., Juhasz G., and Neufeld T.P. Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr. Biol. 17 (2007) 1-11
87. Shacka J.J., Klocke B.J., Young C., Shibata M., Olney J.W., Uchiyama Y., Saftig P., and Roth K.A. Cathepsin D deficiency induces persistent neurodegeneration in the absence of Bax-dependent apoptosis. J. Neurosci. 27 (2007) 2081-2090
88. Shibata M., Lu T., Furuya T., Degterev A., Mizushima N., Yoshimori T., MacDonald M., Yankner B., and Yuan J. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J. Biol. Chem. 281 (2006) 14474-14485
89. Takahashi Y., Coppola D., Matsushita N., Cualing H.D., Sun M., Sato Y., Liang C., Jung J.U., Cheng J.Q., Mul J.J., et al. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat. Cell Biol. 10 (2007) 1142-1151
90. Takacs-Vellai K., Vellai T., Puoti A., Passannante M., Wicky C., Streit A., Kovacs A.L., and Muller F. Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans. Curr. Biol. 15 (2005) 1513-1517
91. Tanaka Y., Gudhe G., Suter A., Eskelinen E.L., Hartmann D., Lullmann-Rauch R., Janssen P.M., Blanz J., von Figura K., and Saftig P. Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature 406 (2000) 902-906
92. Terman A., and Brunk U.T. Autophagy in cardiac myocyte homeostasis, aging, and pathology. Cardiovasc. Res. 68 (2005) 355-365
93. Vesa J., and Peltonen L. Mutated genes in juvenile and variant late infantile neuronal ceroid lipofuscinosis. Curr. Mol. Med. 2 (2002) 439-444
94. Williams A., Jahreiss L., Sarkar S., Saiki S., Menzies F.M., Ravikumar B., and Rubinsztein D.C. Aggregate-prone proteins are cleared from the cytosol by autophagy: therapeutic implications. Curr. Top. Dev. Biol. 76 (2006) 89-101
95. Yorimitsu T., and Klionsky D.J. Eating the endoplasmic reticulum: quality control by autophagy. Trends Cell Biol. 17 (2007) 279-285
96. Yousefi S., Perozzo R., Schmid I., Ziemiecki A., Schaffner T., Scapozza L., Brunner T., and Simon H.U. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat. Cell Biol. 8 (2006) 1124-1132
97. Yu W.H., Cuervo A.M., Kumar A., Peterhoff C.M., Schmidt S.D., Lee J.H., Mohan P.S., Mercken M., Farmery M.R., Tjernberg L.O., et al. Macroautophagy - a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease. J. Cell Biol. 171 (2005) 87-98
98. Yue Z., Horton A., Bravin M., DeJager P.L., Selimi F., and Heintz N. A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice. Neuron 35 (2002) 921-933
99. Yue Z., Jin S., Yang C., Levine A.J., and Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. USA 100 (2003) 15077-15082
100. Zhang Y., Qi H., Taylor R., Xu W., Liu L.F., and Jin S. The role of autophagy in mitochondria maintenance: Characterization of mitochondrial functions in autophagy-deficient S. cerevisiae strains. Autophagy 3 (2007) 337-346
101. Zhu H., Tannous P., Johnstone J.L., Kong Y., Shelton J.M., Richardson J.A., Le V., Levine B., Rothermel B.A., and Hill J.A. Cardiac autophagy is a maladaptive response to hemodynamic stress. J. Clin. Invest. 117 (2007) 1782-1793