Modulation of cell death in age-related diseases

Current Pharmaceutical Design

Volumn 20, Issue 18, 2014, Pages 3052-3067

  Tezil, Tugsan ^a   Basaga, Huveyda ^a  

^a SABANCI UNIVERSITY   (Turkey)

Author keywords

Age related diseases; Aging; Apoptosis; Autophagy; Cancer; Oxidative damage; Programmed cell death

Indexed keywords

ALCOHOL; ALPHA TOCOTRIENOL; ARGININE; BORNEOL; CAFFEIC ACID PHENETHYL ESTER; CATECHIN; CREATINE; DNA; FOLIC ACID; GENISTEIN; HYDROXYTYROSOL; MELATONIN; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; PROTEIN BCL 2; PUERARIN; QUERCETIN; REACTIVE OXYGEN METABOLITE; RESVERATROL; ROSUVASTATIN; SCHIZANDRIN B; SELENIUM; SILYMARIN; SITOSTEROL; SQUALENE; TELOMERASE; VENLAFAXINE; XANTHOPHYLL; XRCC1 PROTEIN; ZEAXANTHIN; ZINC; ANTIOXIDANT; FREE RADICAL;

AGING; ALZHEIMER DISEASE; APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CELL DEATH; DNA DAMAGE; DNA REPAIR; ENZYME ACTIVITY; HUMAN; LIPID PEROXIDATION; MITOCHONDRION; NEOPLASM; NONHUMAN; OXIDATION; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; ANIMAL; HOMEOSTASIS; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

AGING; ANIMALS; ANTIOXIDANTS; APOPTOSIS; AUTOPHAGY; CELL DEATH; FREE RADICALS; HOMEOSTASIS; HUMANS; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 84903714154     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113196660702     Document Type: Article

References (263)

1. Vina J, Borras C, Miquel J. Theories of ageing. IUBMB Life 2007; 59: 249-54.
2. Medvedev ZA. An attempt at a rational classification of theories of ageing. Biol Rev Camb Philos Soc 1990; 65: 375-98.
3. Umansky SR. The genetic program of cell death. Hypothesis and some applications: transformation, carcinogenesis, ageing. J Theor Biol 1982; 97: 591-602.
4. Brown KL, Christenson K, Karlsson A, Dahlgren C, Bylund J. Divergent effects on phagocytosis by macrophage-derived oxygen radicals. J Innate Immun 2009; 1: 592-8.
5. Cutler RG. Human longevity and aging: possible role of reactive oxygen species. Ann N Y Acad Sci 1991; 621: 1-28.
6. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003; 552: 335-44.
7. Brown GC, Borutaite V. There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells. Mitochondrion 2012; 12: 1-4.
8. Starkov AA. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci 2008; 1147: 37-52.
9. Quinlan CL, Orr AL, Perevoshchikova IV, Treberg JR, Ackrell BA, Brand MD. Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions. J Biol Chem 2012.
10. Selivanov VA, Votyakova TV, Pivtoraiko VN, et al. Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain. PLoS Comput Biol 2011; 7: e1001115.
11. Wu Z, Rogers B, Kachi S, Hackett SF, Sick A, Campochiaro PA. Reduction of p66Shc suppresses oxidative damage in retinal pigmented epithelial cells and retina. J Cell Physiol 2006; 209: 996-1005.
12. Paller MS, Jacob HS. Cytochrome P-450 mediates tissue-damaging hydroxyl radical formation during reoxygenation of the kidney. Proc Natl Acad Sci U S A 1994; 91: 7002-6.
13. Woolley JF, Naughton R, Stanicka J, et al. H(2)O(2) Production Downstream of FLT3 Is Mediated by p22phox in the Endoplasmic Reticulum and Is Required for STAT5 Signalling. PLoS One 2012; 7: e34050.
14. Schenkman JB, Jansson I. The many roles of cytochrome b5. Pharmacol Ther 2003; 97: 139-52.
15. Puntarulo S, Cederbaum AI. Role of cytochrome P-450 in the stimulation of microsomal production of reactive oxygen species by ferritin. Biochim Biophys Acta 1996; 1289: 238-46.
16. Kukielka E, Cederbaum AI. Oxidation of ethylene glycol to formaldehyde by rat liver microsomes. Role of cytochrome P-450 and reactive oxygen species. Drug Metab Dispos 1991; 19: 1108-15.
17. Kim S, Sideris DP, Sevier CS, Kaiser CA. Balanced Ero1 activation and inactivation establishes ER redox homeostasis. J Cell Biol 2012; 196: 713-25.
18. Baudhuin P, Mueller M, Poole B, Deduve C. Non-Mitochondrial Oxidizing Particles (Microbodies) in Rat Liver and Kidney and in Tetrahymena Pyriformis. Biochem Biophys Res Commun 1965; 20: 53-9.
19. Boveris A, Oshino N, Chance B. The cellular production of hydrogen peroxide. Biochem J 1972; 128: 617-30.
20. Kukreja RC, Kontos HA, Hess ML, Ellis EF. PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH. Circ Res 1986; 59: 612-9.
21. Roy P, Roy SK, Mitra A, Kulkarni AP. Superoxide generation by lipoxygenase in the presence of NADH and NADPH. Biochim Biophys Acta 1994; 1214: 171-9.
22. O'Donnell VB, Azzi A. High rates of extracellular superoxide generation by cultured human fibroblasts: involvement of a lipidmetabolizing enzyme. Biochem J 1996; 318 (Pt 3): 805-12.
23. McNally JS, Davis ME, Giddens DP, et al. Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress. Am J Physiol Heart Circ Physiol 2003; 285: H2290-7.
24. Desco MC, Asensi M, Marquez R, et al. Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. Diabetes 2002; 51: 1118-24.
25. Lund DD, Chu Y, Miller JD, Heistad DD. Protective effect of extracellular superoxide dismutase on endothelial function during aging. Am J Physiol Heart Circ Physiol 2009; 296: H1920-5.
26. Levin ED. Extracellular superoxide dismutase (EC-SOD) quenches free radicals and attenuates age-related cognitive decline: opportunities for novel drug development in aging. Curr Alzheimer Res 2005; 2: 191-6.
27. Weydert C, Roling B, Liu J, et al. Suppression of the malignant phenotype in human pancreatic cancer cells by the overexpression of manganese superoxide dismutase. Mol Cancer Ther 2003; 2: 361-9.
28. Darby Weydert CJ, Smith BB, Xu L, et al. Inhibition of oral cancer cell growth by adenovirusMnSOD plus BCNU treatment. Free Radic Biol Med 2003; 34: 316-29.
29. Cutler RG. Oxidative stress and aging: catalase is a longevity determinant enzyme. Rejuvenation Res 2005; 8: 138-40.
30. Dai DF, Santana LF, Vermulst M, et al. Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation 2009; 119: 2789-97.
31. Rybka J, Kupczyk D, Kedziora-Kornatowska K, et al. Age-related changes in an antioxidant defense system in elderly patients with essential hypertension compared with healthy controls. Redox Rep 2011; 16: 71-7.
32. Fabian E, Bogner M, Elmadfa I. Age-related modification of antioxidant enzyme activities in relation to cardiovascular risk factors. Eur J Clin Invest 2012; 42: 42-8.
33. Rizvi SI, Maurya PK. Alterations in antioxidant enzymes during aging in humans. Mol Biotechnol 2007; 37: 58-61.
34. Dizdaroglu M. Oxidatively induced DNA damage: Mechanisms, repair and disease. Cancer Lett 2012.
35. Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H. Free radicalinduced damage to DNA: mechanisms and measurement. Free Radic Biol Med 2002; 32: 1102-15.
36. Madison AL, Perez ZA, To P, et al. Dependence of DNA-protein cross-linking via guanine oxidation upon local DNA sequence as studied by restriction endonuclease inhibition. Biochemistry 2012; 51: 362-9.
37. Xu X, Muller JG, Ye Y, Burrows CJ. DNA-protein cross-links between guanine and lysine depend on the mechanism of oxidation for formation of C5 vs C8 guanosine adducts. J Am Chem Soc 2008; 130: 703-9.
38. Gan W, Nie B, Shi F, et al. Age-dependent increases in the oxidative damage of DNA, RNA, and their metabolites in normal and senescence-accelerated mice analyzed by LC-MS/MS: urinary 8-oxoguanosine as a novel biomarker of aging. Free Radic Biol Med 2012; 52: 1700-7.
39. Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 2003; 17: 1195-214.
40. Lindahl T. Instability and decay of the primary structure of DNA. Nature 1993; 362: 709-15.
41. Lindahl T, Karran P, Wood RD. DNA excision repair pathways. Curr Opin Genet Dev 1997; 7: 158-69.
42. Odell ID, Wallace SS, Pederson DS. Rules of engagement for base excision repair in chromatin. J Cell Physiol 2012.
43. Robertson AB, Klungland A, Rognes T, Leiros I. DNA repair in mammalian cells: Base excision repair: the long and short of it. Cell Mol Life Sci 2009; 66: 981-93.
44. Hegde ML, Hazra TK, Mitra S. Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res 2008; 18: 27-47.
45. Swain U, Rao KS. Age-dependent decline of DNA base excision repair activity in rat cortical neurons. Mech Ageing Dev 2012; 133: 186-94.
46. Wang JL, Wang PC. The effect of aging on the DNA damage and repair capacity in 2BS cells undergoing oxidative stress. Mol Biol Rep 2012; 39: 233-41.
47. Swain U, Subba Rao K. Study of DNA damage via the comet assay and base excision repair activities in rat brain neurons and astrocytes during aging. Mech Ageing Dev 2011; 132: 374-81.
48. Vyjayanti VN, Swain U, Rao KS. Age-related decline in DNA polymerase beta activity in rat brain and tissues. Neurochem Res 2012; 37: 991-5.
49. Amouroux R, Campalans A, Epe B, Radicella JP. Oxidative stress triggers the preferential assembly of base excision repair complexes on open chromatin regions. Nucleic Acids Res 2010; 38: 2878-90.
50. Woodbine L, Brunton H, Goodarzi AA, Shibata A, Jeggo PA. Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated and Artemis for their repair. Nucleic Acids Res 2011; 39: 6986-97.
51. Goodarzi AA, Noon AT, Deckbar D, et al. ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell 2008; 31: 167-77.
52. Yuan T, Wei J, Luo J, Liu M, Deng S, Chen P. Polymorphisms of Base-Excision Repair Genes hOGG1 326cys and XRCC1 280His Increase Hepatocellular Carcinoma Risk. Dig Dis Sci 2012.
53. Mahjabeen I, Masood N, Baig RM, et al. Novel mutations of OGG1 base excision repair pathway gene in laryngeal cancer patients. Fam Cancer 2012.
54. Nakao M, Hosono S, Ito H, et al. Selected Polymorphisms of Base Excision Repair Genes and Pancreatic Cancer Risk in Japanese. J Epidemiol 2012.
55. Mittal RD, Mandal RK, Gangwar R. Base excision repair pathway genes polymorphism in prostate and bladder cancer risk in North Indian population. Mech Ageing Dev 2012; 133: 127-32.
56. Bhusari SS, Dobosy JR, Fu V, Almassi N, Oberley T, Jarrard DF. Superoxide dismutase 1 knockdown induces oxidative stress and DNA methylation loss in the prostate. Epigenetics 2010; 5: 402-9.
57. Castro Mdel R, Suarez E, Kraiselburd E, et al. Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys. Exp Gerontol 2012; 47: 29-37.
58. Haendeler J, Drose S, Buchner N, et al. Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage. Arterioscler Thromb Vasc Biol 2009; 29: 929-35.
59. Liu CM, Ma JQ, Sun YZ. Puerarin protects the rat liver against oxidative stress-mediated DNA damage and apoptosis induced by lead. Exp Toxicol Pathol 2012; 64: 575-82.
60. Horvathova E, Kozics K, Srancikova A, et al. Borneol administration protects primary rat hepatocytes against exogenous oxidative DNA damage. Mutagenesis 2012.
61. Warleta F, Quesada CS, Campos M, Allouche Y, Beltran G, Gaforio JJ. Hydroxytyrosol protects against oxidative DNA damage in human breast cells. Nutrients 2011; 3: 839-57.
62. Ilavarasi K, Kiruthiga PV, Pandian SK, Devi KP. Hydroxytyrosol, the phenolic compound of olive oil protects human PBMC against oxidative stress and DNA damage mediated by 2,3,7,8-TCDD. Chemosphere 2011; 84: 888-93.
63. Zhang X, Cao J, Jiang L, Geng C, Zhong L. Protective effect of hydroxytyrosol against acrylamide-induced cytotoxicity and DNA damage in HepG2 cells. Mutat Res 2009; 664: 64-8.
64. Taridi NM, Yahaya MF, Teoh SL, et al. Tocotrienol rich fraction (TRF) supplementation protects against oxidative DNA damage and improves cognitive functions in Wistar rats. Clin Ter 2011; 162: 93-8.
65. Abdel-Wahab BA, Salama RH. Venlafaxine protects against stressinduced oxidative DNA damage in hippocampus during antidepressant testing in mice. Pharmacol Biochem Behav 2011; 100: 59-65.
66. Liu CM, Ma JQ, Sun YZ. Quercetin protects the rat kidney against oxidative stress-mediated DNA damage and apoptosis induced by lead. Environ Toxicol Pharmacol 2010; 30: 264-71.
67. Warleta F, Campos M, Allouche Y, et al. Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial cells but not in MCF7 and MDA-MB-231 human breast cancer cells. Food Chem Toxicol 2010; 48: 1092-100.
68. Leung HY, Yung LH, Poon CH, Shi G, Lu AL, Leung LK. Genistein protects against polycyclic aromatic hydrocarboninduced oxidative DNA damage in non-cancerous breast cells MCF-10A. Br J Nutr 2009; 101: 257-62.
69. Wu HJ, Chan WH. Genistein protects methylglyoxal-induced oxidative DNA damage and cell injury in human mononuclear cells. Toxicol In vitro 2007; 21: 335-42.
70. Raschke M, Rowland IR, Magee PJ, Pool-Zobel BL. Genistein protects prostate cells against hydrogen peroxide-induced DNA damage and induces expression of genes involved in the defence against oxidative stress. Carcinogenesis 2006; 27: 2322-30.
71. Schupp N, Schmid U, Heidland A, Stopper H. Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis. Atherosclerosis 2008; 199: 278-87.
72. Esrefoglu MP, Iraz MAP, Ates BAP, Gul MAP. Not Only Melatonin but also Caffeic Acid Phenethyl Ester Protects Kidneys against Aging-related Oxidative Damage in Sprague Dawley Rats. Ultrastruct Pathol 2012; 36: 244-251.
73. Yu SL, Lin SB, Yu YL, et al. Isochaihulactone protects PC12 cell against H(2)O(2) induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model. Acta Pharmacol Sin 2010; 31: 1532-40.
74. Katiyar SK, Mantena SK, Meeran SM. Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced apoptosis and DNA damage by nucleotide excision repair mechanism. PLoS One 2011; 6: e21410.
75. Serpeloni JM, Barcelos GR, Friedmann Angeli JP, et al. Dietary carotenoid lutein protects against DNA damage and alterations of the redox status induced by cisplatin in human derived HepG2 cells. Toxicol In vitro 2012; 26: 288-94.
76. Cui Y, Gao CQ, Sun G, et al. L-arginine promotes DNA repair in cultured bronchial epithelial cells exposed to ozone: involvement of the ATM pathway. Cell Biol Int 2011; 35: 273-80.
77. Spanier G, Xu H, Xia N, et al. Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol 2009; 60 Suppl 4: 111-6.
78. Babizhayev MA, Savel'yeva EL, Moskvina SN, Yegorov YE. Telomere length is a biomarker of cumulative oxidative stress, biologic age, and an independent predictor of survival and therapeutic treatment requirement associated with smoking behavior. Am J Ther 2011; 18: e209-26.
79. Collins AR. Investigating oxidative DNA damage and its repair using the comet assay. Mutat Res 2009; 681: 24-32.
80. Valdes AM, Andrew T, Gardner JP, et al. Obesity, cigarette smoking, and telomere length in women. Lancet 2005; 366: 662-4.
81. Voghel G, Thorin-Trescases N, Mamarbachi AM, et al. Endogenous oxidative stress prevents telomerase-dependent immortalization of human endothelial cells. Mech Ageing Dev 2010; 131: 354-63.
82. Ju Z, Zhang J, Gao Y, Cheng T. Telomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging. Int J Hematol 2011; 94: 33-43.
83. Mattiussi M, Tilman G, Lenglez S, Decottignies A. Human telomerase represses ROS-dependent cellular responses to Tumor Necrosis Factor-alpha without affecting NF-kappaB activation. Cell Signal 2012; 24: 708-17.
84. Nitta E, Yamashita M, Hosokawa K, et al. Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism. Blood 2011; 117: 4169-80.
85. Wu X, Amos CI, Zhu Y, et al. Telomere dysfunction: a potential cancer predisposition factor. J Natl Cancer Inst 2003; 95: 1211-8.
86. Doshida M, Ohmichi M, Tsutsumi S, et al. Raloxifene increases proliferation and up-regulates telomerase activity in human umbilical vein endothelial cells. J Biol Chem 2006; 281: 24270-8.
87. Bader A, Petters O, Keller M, Pavlica S. Paracetamol treatment increases telomerase activity in rat embryonic liver cells. Pharmacol Rep 2011; 63: 1435-41.
88. Zhu H, Guo D, Li K, et al. Increased telomerase activity and vitamin D supplementation in overweight African Americans. Int J Obes (Lond) 2012; 36: 805-9.
89. Kim YY, Ku SY, Huh Y, et al. Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes. Age (Dordr) 2012.
90. Makpol S, Abidin AZ, Sairin K, Mazlan M, Top GM, Ngah WZ. gamma-Tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals. Oxid Med Cell Longev 2010; 3: 35-43.
91. Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells. Cancer Detect Prev 2007; 31: 119-28.
92. Nakagawa K, Eitsuka T, Inokuchi H, Miyazawa T. DNA chip analysis of comprehensive food function: inhibition of angiogenesis and telomerase activity with unsaturated vitamin E, tocotrienol. Biofactors 2004; 21: 5-10.
93. Bernardes de Jesus B, Vera E, Schneeberger K, et al. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med 2012; 4: 691-704.
94. Grune T, Shringarpure R, Sitte N, Davies K. Age-related changes in protein oxidation and proteolysis in mammalian cells. J Gerontol A Biol Sci Med Sci 2001; 56: B459-67.
95. Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 1997; 272: 20313-6.
96. Stadtman ER, Van Remmen H, Richardson A, Wehr NB, Levine RL. Methionine oxidation and aging. Biochim Biophys Acta 2005; 1703: 135-40.
97. Grune T, Reinheckel T, Davies KJ. Degradation of oxidized proteins in mammalian cells. FASEB J 1997; 11: 526-34.
98. De Luca A, Sanna F, Sallese M, et al. Methionine sulfoxide reductase A down-regulation in human breast cancer cells results in a more aggressive phenotype. Proc Natl Acad Sci U S A 2010; 107: 18628-33.
99. Moskovitz J, Bar-Noy S, Williams WM, Requena J, Berlett BS, Stadtman ER. Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals. Proc Natl Acad Sci U S A 2001; 98: 12920-5.
100. Wassef R, Haenold R, Hansel A, Brot N, Heinemann SH, Hoshi T. Methionine sulfoxide reductase A and a dietary supplement Smethyl-L-cysteine prevent Parkinson's-like symptoms. J Neurosci 2007; 27: 12808-16.
101. Kurepa J, Smalle JA. To misfold or to lose structure?: Detection and degradation of oxidized proteins by the 20S proteasome. Plant Signal Behav 2008; 3: 386-8.
102. Kastle M, Grune T. Proteins bearing oxidation-induced carbonyl groups are not preferentially ubiquitinated. Biochimie 2011; 93: 1076-9.
103. Kastle M, Grune T. Protein oxidative modification in the aging organism and the role of the ubiquitin proteasomal system. Curr Pharm Des 2011; 17: 4007-22.
104. Beal MF. Oxidatively modified proteins in aging and disease. Free Radic Biol Med 2002; 32: 797-803.
105. Zhu X, Raina AK, Lee HG, Casadesus G, Smith MA, Perry G. Oxidative stress signalling in Alzheimer's disease. Brain Res 2004; 1000: 32-9.
106. Pratico D. Alzheimer's disease and oxygen radicals: new insights. Biochem Pharmacol 2002; 63: 563-7.
107. Aslan M, Ozben T. Reactive oxygen and nitrogen species in Alzheimer's disease. Curr Alzheimer Res 2004; 1: 111-9.
108. Fan Q, Chen M, Fang X, et al. Aging might augment reactive oxygen species (ROS) formation and affect reactive nitrogen species (RNS) level after myocardial ischemia/reperfusion in both humans and rats. Age (Dordr) 2012.
109. Pignatelli B, Li CQ, Boffetta P, et al. Nitrated and oxidized plasma proteins in smokers and lung cancer patients. Cancer Res 2001; 61: 778-84.
110. McCormack AL, Mak SK, Di Monte DA. Increased alphasynuclein phosphorylation and nitration in the aging primate substantia nigra. Cell Death Dis 2012; 3: e315.
111. Marnett LJ. Lipid peroxidation-DNA damage by malondialdehyde. Mutat Res 1999; 424: 83-95.
112. Li G, Chen Y, Hu H, et al. Association between age-related decline of kidney function and plasma malondialdehyde. Rejuvenation Res 2012; 15: 257-64.
113. Jia L, Dong Y, Yang H, Pan X, Fan R, Zhai L. Serum superoxide dismutase and malondialdehyde levels in a group of Chinese patients with age-related macular degeneration. Aging Clin Exp Res 2011; 23: 264-7.
114. Yoval-Sanchez B, Rodriguez-Zavala JS. Differences in susceptibility to inactivation of human aldehyde dehydrogenases by lipid peroxidation byproducts. Chem Res Toxicol 2012; 25: 722-9.
115. Kahlert C, Bergmann F, Beck J, et al. Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer. BMC Cancer 2011; 11: 275.
116. Li T, Su Y, Mei Y, et al. ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome. Lab Invest 2010; 90: 234-44.
117. Ojeda ML, Barrero MJ, Nogales F, Murillo ML, Carreras O. Oxidative effects of chronic ethanol consumption on the functions of heart and kidney: folic acid supplementation. Alcohol Alcohol 2012; 47: 404-12.
118. Kim MY, Kim EJ, Kim YN, Choi C, Lee BH. Effects of alphalipoic acid and L-carnosine supplementation on antioxidant activities and lipid profiles in rats. Nutr Res Pract 2011; 5: 421-8.
119. Cheng YT, Wu CH, Ho CY, Yen GC. Catechin protects against ketoprofen-induced oxidative damage of the gastric mucosa by upregulating Nrf2 in vitro and in vivo. J Nutr Biochem 2012.
120. Tabassum H, Parvez S, Rehman H, Banerjee BD, Raisuddin S. Catechin as an antioxidant in liver mitochondrial toxicity: Inhibition of tamoxifen-induced protein oxidation and lipid peroxidation. J Biochem Mol Toxicol 2007; 21: 110-7.
121. Baskar AA, Al Numair KS, Gabriel Paulraj M, Alsaif MA, Muamar MA, Ignacimuthu S. beta-sitosterol prevents lipid peroxidation and improves antioxidant status and histoarchitecture in rats with 1,2-dimethylhydrazine-induced colon cancer. J Med Food 2012; 15: 335-43.
122. Chen N, Ko M. Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts. Biol Pharm Bull 2010; 33: 825-9.
123. Giridharan VV, Thandavarayan RA, Sato S, Ko KM, Konishi T. Prevention of scopolamine-induced memory deficits by schisandrin B, an antioxidant lignan from Schisandra chinensis in mice. Free Radic Res 2011; 45: 950-8.
124. Ko KM, Lam BY. Schisandrin B protects against tertbutylhydroperoxide induced cerebral toxicity by enhancing glutathione antioxidant status in mouse brain. Mol Cell Biochem 2002; 238: 181-6.
125. Akil M, Bicer M, Menevse E, Baltaci AK, Mogulkoc R. Selenium supplementation prevents lipid peroxidation caused by arduous exercise in rat brain tissue. Bratisl Lek Listy 2011; 112: 314-7.
126. Schimel AM, Abraham L, Cox D, et al. N-acetylcysteine amide (NACA) prevents retinal degeneration by up-regulating reduced glutathione production and reversing lipid peroxidation. Am J Pathol 2011; 178: 2032-43.
127. Shen KP, Lin HL, Hsieh SL, Kwan AL, Chen IJ, Wu BN. Eugenosedin-A prevents hyperglycaemia, hyperlipidaemia and lipid peroxidation in C57BL/6J mice fed a high-fat diet. J Pharm Pharmacol 2009; 61: 517-25.
128. Rahimi R. Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise. J Strength Cond Res 2011; 25: 3448-55.
129. Bao B, Prasad AS, Beck FW, et al. Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr 2010; 91: 1634-41.
130. Akbulut KG, Gonul B, Akbulut H. Exogenous melatonin decreases age-induced lipid peroxidation in the brain. Brain Res 2008; 1238: 31-5.
131. Huang TC, Lu KT, Wo YY, Wu YJ, Yang YL. Resveratrol protects rats from Abeta-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation. PLoS One 2011; 6: e29102.
132. Franco JG, de Moura EG, Koury JC, et al. Resveratrol reduces lipid peroxidation and increases sirtuin 1 expression in adult animals programmed by neonatal protein restriction. J Endocrinol 2010; 207: 319-28.
133. Pandey KB, Rizvi SI. Protective effect of resveratrol on formation of membrane protein carbonyls and lipid peroxidation in erythrocytes subjected to oxidative stress. Appl Physiol Nutr Metab 2009; 34: 1093-7.
134. Okutan H, Ozcelik N, Yilmaz HR, Uz E. Effects of caffeic acid phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic rat heart. Clin Biochem 2005; 38: 191-6.
135. Yilmaz HR, Uz E, Yucel N, Altuntas I, Ozcelik N. Protective effect of caffeic acid phenethyl ester (CAPE) on lipid peroxidation and antioxidant enzymes in diabetic rat liver. J Biochem Mol Toxicol 2004; 18: 234-8.
136. Farombi EO, Abarikwu SO, Adesiyan AC, Oyejola TO. Quercetin exacerbates the effects of subacute treatment of atrazine on reproductive tissue antioxidant defence system, lipid peroxidation and sperm quality in rats. Andrologia 2012.
137. Gao S, Qin T, Liu Z, et al. Lutein and zeaxanthin supplementation reduces H2O2-induced oxidative damage in human lens epithelial cells. Mol Vis 2011; 17: 3180-90.
138. Zamzami N, Susin SA, Marchetti P, et al. Mitochondrial control of nuclear apoptosis. J Exp Med 1996; 183: 1533-44.
139. Kroemer G, Petit P, Zamzami N, Vayssiere JL, Mignotte B. The biochemistry of programmed cell death. FASEB J 1995; 9: 1277-87.
140. Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996; 86: 147-57.
141. Gonzalvez F, Gottlieb E. Cardiolipin: setting the beat of apoptosis. Apoptosis 2007; 12: 877-85.
142. Kagan VE, Tyurin VA, Jiang J, et al. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol 2005; 1: 223-32.
143. Sakurai K, Katoh M, Fujimoto Y. Alloxan-induced mitochondrial permeability transition triggered by calcium, thiol oxidation, and matrix ATP. J Biol Chem 2001; 276: 26942-6.
144. Gottlieb RA. Mitochondria: execution central. FEBS Lett 2000; 482: 6-12.
145. Szabo I, Zoratti M. The mitochondrial permeability transition pore may comprise VDAC molecules. I. Binary structure and voltage dependence of the pore. FEBS Lett 1993; 330: 201-5.
146. Baumgartner HK, Gerasimenko JV, Thorne C, et al. Calcium elevation in mitochondria is the main Ca2+ requirement for mitochondrial permeability transition pore (mPTP) opening. J Biol Chem 2009; 284: 20796-803.
147. Kowaltowski AJ, Vercesi AE, Castilho RF. Mitochondrial membrane protein thiol reactivity with N-ethylmaleimide or mersalyl is modified by Ca2+: correlation with mitochondrial permeability transition. Biochim Biophys Acta 1997; 1318: 395-402.
148. Jones A. Does the plant mitochondrion integrate cellular stress and regulate programmed cell death? Trends Plant Sci 2000; 5: 225-30.
149. Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 2007; 9: 550-5.
150. Kumarswamy R, Chandna S. Putative partners in Bax mediated cytochrome-c release: ANT, CypD, VDAC or none of them? Mitochondrion 2009; 9: 1-8.
151. Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 1984; 226: 1097-9.
152. Cory S, Adams JM. The Bcl2 family: regulators of the cellular lifeor-death switch. Nat Rev Cancer 2002; 2: 647-56.
153. Kutuk O, Basaga H. Bcl-2 protein family: implications in vascular apoptosis and atherosclerosis. Apoptosis 2006; 11: 1661-75.
154. Hsu YT, Wolter KG, Youle RJ. Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. Proc Natl Acad Sci U S A 1997; 94: 3668-72.
155. Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG, Youle RJ. Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol 1997; 139: 1281-92.
156. Antonsson B, Montessuit S, Sanchez B, Martinou JC. Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J Biol Chem 2001; 276: 11615-23.
157. Griffiths GJ, Dubrez L, Morgan CP, et al. Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis. J Cell Biol 1999; 144: 903-14.
158. Bellosillo B, Villamor N, Lopez-Guillermo A, et al. Spontaneous and drug-induced apoptosis is mediated by conformational changes of Bax and Bak in B-cell chronic lymphocytic leukemia. Blood 2002; 100: 1810-6.
159. Pang YP, Dai H, Smith A, Meng XW, Schneider PA, Kaufmann SH. Bak Conformational Changes Induced by Ligand Binding: Insight into BH3 Domain Binding and Bak Homo-Oligomerization. Sci Rep 2012; 2: 257.
160. Walensky LD, Gavathiotis E. BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore. Trends Biochem Sci 2011; 36: 642-52.
161. Nouraini S, Six E, Matsuyama S, Krajewski S, Reed JC. The putative pore-forming domain of Bax regulates mitochondrial localization and interaction with Bcl-X(L). Mol Cell Biol 2000; 20: 1604-15.
162. Mikhailov V, Mikhailova M, Degenhardt K, Venkatachalam MA, White E, Saikumar P. Association of Bax and Bak homo-oligomers in mitochondria. Bax requirement for Bak reorganization and cytochrome c release. J Biol Chem 2003; 278: 5367-76.
163. Mikhailov V, Mikhailova M, Pulkrabek DJ, Dong Z, Venkatachalam MA, Saikumar P. Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J Biol Chem 2001; 276: 18361-74.
164. Goldstein JC, Waterhouse NJ, Juin P, Evan GI, Green DR. The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant. Nat Cell Biol 2000; 2: 156-62.
165. Rehm M, Dussmann H, Prehn JH. Real-time single cell analysis of Smac/DIABLO release during apoptosis. J Cell Biol 2003; 162: 1031-43.
166. Kim H, Rafiuddin-Shah M, Tu HC, et al. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat Cell Biol 2006; 8: 1348-58.
167. Willis SN, Fletcher JI, Kaufmann T, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 2007; 315: 856-9.
168. Riedl SJ, Salvesen GS. The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol 2007; 8: 405-13.
169. Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW. Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol Cell 2002; 9: 423-32.
170. Yuan S, Yu X, Topf M, Ludtke SJ, Wang X, Akey CW. Structure of an apoptosome-procaspase-9 CARD complex. Structure 2010; 18: 571-83.
171. Hu Y, Ding L, Spencer DM, Nunez G. WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation. J Biol Chem 1998; 273: 33489-94.
172. Yuan S, Yu X, Asara JM, Heuser JE, Ludtke SJ, Akey CW. The holo-apoptosome: activation of procaspase-9 and interactions with caspase-3. Structure 2011; 19: 1084-96.
173. McGrath LB, Onnis V, Campiani G, Williams DC, Zisterer DM, Mc Gee MM. Caspase-activated DNase (CAD)-independent oligonucleosomal DNA fragmentation in chronic myeloid leukaemia cells; a requirement for serine protease and Mn2+-dependent acidic endonuclease activity. Apoptosis 2006; 11: 1473-87.
174. Lu H, Hou Q, Zhao T, et al. Granzyme M directly cleaves inhibitor of caspase-activated DNase (CAD) to unleash CAD leading to DNA fragmentation. J Immunol 2006; 177: 1171-8.
175. Sakahira H, Enari M, Nagata S. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 1998; 391: 96-9.
176. Chan KT, Cortesio CL, Huttenlocher A. FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasion. J Cell Biol 2009; 185: 357-70.
177. Bokoch GM. Caspase-mediated activation of PAK2 during apoptosis: proteolytic kinase activation as a general mechanism of apoptotic signal transduction? Cell Death Differ 1998; 5: 637-45.
178. Verhoven B, Schlegel RA, Williamson P. Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes. J Exp Med 1995; 182: 1597-601.
179. Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 2009; 335: 1-32.
180. Cuervo AM. Autophagy: in sickness and in health. Trends Cell Biol 2004; 14: 70-7.
181. Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 2004; 6: 463-77.
182. Orenstein SJ, Cuervo AM. Chaperone-mediated autophagy: molecular mechanisms and physiological relevance. Semin Cell Dev Biol 2010; 21: 719-26.
183. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004; 18: 1926-45.
184. Beevers CS, Li F, Liu L, Huang S. Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells. Int J Cancer 2006; 119: 757-64.
185. Nobukuni T, Joaquin M, Roccio M, et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci U S A 2005; 102: 14238-43.
186. Wang L, Harris TE, Roth RA, Lawrence JC, Jr. PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding. J Biol Chem 2007; 282: 20036-44.
187. Sancak Y, Thoreen CC, Peterson TR, et al. PRAS40 is an insulinregulated inhibitor of the mTORC1 protein kinase. Mol Cell 2007; 25: 903-15.
188. Kim DH, Sarbassov DD, Ali SM, et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 2002; 110: 163-75.
189. Kim DH, Sarbassov DD, Ali SM, et al. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient sensitive interaction between raptor and mTOR. Mol Cell 2003; 11: 895-904.
190. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006; 124: 471-84.
191. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 2010; 141: 290-303.
192. Levine B, Sinha S, Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 2008; 4: 600-6.
193. Botti J, Djavaheri-Mergny M, Pilatte Y, Codogno P. Autophagy signaling and the cogwheels of cancer. Autophagy 2006; 2: 67-73.
194. Gwinn DM, Shackelford DB, Egan DF, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 2008; 30: 214-26.
195. Egan D, Kim J, Shaw RJ, Guan KL. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy 2011; 7: 643-4.
196. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol 2010; 22: 132-9.
197. Cheong H, Lindsten T, Wu J, Lu C, Thompson CB. Ammoniainduced autophagy is independent of ULK1/ULK2 kinases. Proc Natl Acad Sci U S A 2011; 108: 11121-6.
198. Alers S, Loffler AS, Paasch F, et al. Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction. Autophagy 2011; 7: 1423-33.
199. Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005; 122: 927-39.
200. Park KJ, Lee SH, Lee CH, et al. Upregulation of Beclin-1 expression and phosphorylation of Bcl-2 and p53 are involved in the JNK-mediated autophagic cell death. Biochem Biophys Res Commun 2009; 382: 726-9.
201. Oberstein A, Jeffrey PD, Shi Y. Crystal structure of the Bcl-XLBeclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. J Biol Chem 2007; 282: 13123-32.
202. Erlich S, Mizrachy L, Segev O, et al. Differential interactions between Beclin 1 and Bcl-2 family members. Autophagy 2007; 3: 561-8.
203. Fan W, Nassiri A, Zhong Q. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). Proc Natl Acad Sci U S A 2011; 108: 7769-74.
204. Itakura E, Mizushima N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy 2010; 6: 764-76.
205. Polson HE, de Lartigue J, Rigden DJ, et al. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy 2010; 6.
206. Nobel Prize in Chemistry 2004. Aaron Ciechanover, Avram Hershko and Irwin Rose. Indian J Physiol Pharmacol 2005; 49: 121.
207. Mizushima N, Noda T, Yoshimori T, et al. A protein conjugation system essential for autophagy. Nature 1998; 395: 395-8.
208. Shintani T, Mizushima N, Ogawa Y, Matsuura A, Noda T, Ohsumi Y. Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast. EMBO J 1999; 18: 5234-41.
209. Mizushima N, Noda T, Ohsumi Y. Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. EMBO J 1999; 18: 3888-96.
210. Kuma A, Mizushima N, Ishihara N, Ohsumi Y. Formation of the approximately 350-kDa Apg12-Apg5. Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J Biol Chem 2002; 277: 18619-25.
211. Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell 2008; 19: 2092-100.
212. Geng J, Baba M, Nair U, Klionsky DJ. Quantitative analysis of autophagy-related protein stoichiometry by fluorescence microscopy. J Cell Biol 2008; 182: 129-40.
213. Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci 2004; 117: 2805-12.
214. Ichimura Y, Kirisako T, Takao T, et al. A ubiquitin-like system mediates protein lipidation. Nature 2000; 408: 488-92.
215. Hanada T, Noda NN, Satomi Y, et al. The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem 2007; 282: 37298-302.
216. Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000; 19: 5720-8.
217. Geng J, Klionsky DJ. The Golgi as a potential membrane source for autophagy. Autophagy 2010; 6: 950-1.
218. Hailey DW, Rambold AS, Satpute-Krishnan P, et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 2010; 141: 656-67.
219. Ravikumar B, Moreau K, Rubinsztein DC. Plasma membrane helps autophagosomes grow. Autophagy 2010; 6: 1184-6.
220. Tabata K, Matsunaga K, Sakane A, Sasaki T, Noda T, Yoshimori T. Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain. Mol Biol Cell 2010; 21: 4162-72.
221. Militello RD, Colombo MI. A membrane is born: origin of the autophagosomal compartment. Curr Mol Med 2011; 11: 197-203.
222. Tooze SA, Yoshimori T. The origin of the autophagosomal membrane. Nat Cell Biol 2010; 12: 831-5.
223. Axe EL, Walker SA, Manifava M, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 2008; 182: 685-701.
224. 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: 671-82.
225. Shen J, Tower J. Programmed cell death and apoptosis in aging and life span regulation. Discov Med 2009; 8: 223-6.
226. Aita VM, Liang XH, Murty VV, et al. Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics 1999; 59: 59-65.
227. Liang XH, Jackson S, Seaman M, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672-6.
228. Inoue K, Kohno T, Takakura S, Hayashi Y, Mizoguchi H, Yokota J. Frequent microsatellite instability and BAX mutations in T cell acute lymphoblastic leukemia cell lines. Leuk Res 2000; 24: 255-62.
229. Miquel C, Borrini F, Grandjouan S, et al. Role of bax mutations in apoptosis in colorectal cancers with microsatellite instability. Am J Clin Pathol 2005; 123: 562-70.
230. Shibata MA, Liu ML, Knudson MC, et al. Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage. EMBO J 1999; 18: 2692-701.
231. Kondo S, Shinomura Y, Miyazaki Y, et al. Mutations of the bak gene in human gastric and colorectal cancers. Cancer Res 2000; 60: 4328-30.
232. Ke F, Voss A, Kerr JB, et al. BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice. Cell Death Differ 2012; 19: 915-25.
233. O'Reilly LA, Strasser A. Apoptosis and autoimmune disease. Inflamm Res 1999; 48: 5-21.
234. Zinkel SS, Ong CC, Ferguson DO, et al. Proapoptotic BID is required for myeloid homeostasis and tumor suppression. Genes Dev 2003; 17: 229-39.
235. Lee JH, Soung YH, Lee JW, et al. Inactivating mutation of the proapoptotic gene BID in gastric cancer. J Pathol 2004; 202: 439-45.
236. Zhang H, Bosch-Marce M, Shimoda LA, et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 2008; 283: 10892-903.
237. Li B, Dou QP. Bax degradation by the ubiquitin/proteasomedependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci U S A 2000; 97: 3850-5.
238. Chang YC, Lee YS, Tejima T, et al. mdm2 and bax, downstream mediators of the p53 response, are degraded by the ubiquitinproteasome pathway. Cell Growth Differ 1998; 9: 79-84.
239. Breitschopf K, Zeiher AM, Dimmeler S. Ubiquitin-mediated degradation of the proapoptotic active form of bid. A functional consequence on apoptosis induction. J Biol Chem 2000; 275: 21648-52.
240. Zhong Q, Gao W, Du F, Wang X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell 2005; 121: 1085-95.
241. Moungjaroen J, Nimmannit U, Callery PS, et al. Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 downregulation. J Pharmacol Exp Ther 2006; 319: 1062-9.
242. Shan YX, Liu TJ, Su HF, Samsamshariat A, Mestril R, Wang PH. Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signaling induced by doxorubicin in cardiac muscle cells. J Mol Cell Cardiol 2003; 35: 1135-43.
243. Deng X, Ruvolo P, Carr B, May WS, Jr. Survival function of ERK1/2 as IL-3-activated, staurosporine-resistant Bcl2 kinases. Proc Natl Acad Sci U S A 2000; 97: 1578-83.
244. Breitschopf K, Haendeler J, Malchow P, Zeiher AM, Dimmeler S. Posttranslational modification of Bcl-2 facilitates its proteasomedependent degradation: molecular characterization of the involved signaling pathway. Mol Cell Biol 2000; 20: 1886-96.
245. Domina AM, Vrana JA, Gregory MA, Hann SR, Craig RW. MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol. Oncogene 2004; 23: 5301-15.
246. Kobayashi S, Lee SH, Meng XW, et al. Serine 64 phosphorylation enhances the antiapoptotic function of Mcl-1. J Biol Chem 2007; 282: 18407-17.
247. Kutuk O, Letai A. Regulation of Bcl-2 family proteins by posttranslational modifications. Curr Mol Med 2008; 8: 102-18.
248. Ruggiero FM, Cafagna F, Petruzzella V, Gadaleta MN, Quagliariello E. Lipid composition in synaptic and nonsynaptic mitochondria from rat brains and effect of aging. J Neurochem 1992; 59: 487-91.
249. Bayir H, Fadeel B, Palladino MJ, et al. Apoptotic interactions of cytochrome c: redox flirting with anionic phospholipids within and outside of mitochondria. Biochim Biophys Acta 2006; 1757: 648-59.
250. Beal MF. Mitochondria, oxidative damage, and inflammation in Parkinson's disease. Ann N Y Acad Sci 2003; 991: 120-31.
251. Calissano P, Matrone C, Amadoro G. Apoptosis and in vitro Alzheimer disease neuronal models. Commun Integr Biol 2009; 2: 163-9.
252. Jaeger PA, Wyss-Coray T. Beclin 1 complex in autophagy and Alzheimer disease. Arch Neurol 2010; 67: 1181-4.
253. Winslow AR, Rubinsztein DC. The Parkinson disease protein alpha-synuclein inhibits autophagy. Autophagy 2011; 7: 429-31.
254. Yang Q, Mao Z. Parkinson disease: a role for autophagy? Neuroscientist 2010; 16: 335-41.
255. Shang L, Chen S, Du F, Li S, Zhao L, Wang X. Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc Natl Acad Sci U S A 2011; 108: 4788-93.
256. Furuya T, Kim M, Lipinski M, et al. Negative regulation of Vps34 by Cdk mediated phosphorylation. Mol Cell 2010; 38: 500-11.
257. Dhavan R, Tsai LH. A decade of CDK5. Nat Rev Mol Cell Biol 2001; 2: 749-59.
258. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 2009; 9: 153-66.
259. Cherra SJ, 3rd, Kulich SM, Uechi G, et al. Regulation of the autophagy protein LC3 by phosphorylation. J Cell Biol 2010; 190: 533-9.
260. Zalckvar E, Berissi H, Eisenstein M, Kimchi A. Phosphorylation of Beclin 1 by DAP-kinase promotes autophagy by weakening its interactions with Bcl-2 and Bcl-XL. Autophagy 2009; 5: 720-2.
261. Wu PR, Tsai PI, Chen GC, et al. DAPK activates MARK1/2 to regulate microtubule assembly, neuronal differentiation, and tau toxicity. Cell Death Differ 2011; 18: 1507-20.
262. Lucking CB, Durr A, Bonifati V, et al. Association between earlyonset Parkinson's disease and mutations in the parkin gene. N Engl J Med 2000; 342: 1560-7.
263. Degregori J. Challenging the axiom: does the occurrence of oncogenic mutations truly limit cancer development with age? Oncogene 2012.