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Abstract

Alterations of mitochondrial functions are linked to multiple degenerative or acute diseases. As mitochondria age in our cells, they become progressively inefficient and potentially toxic, and acute damage can trigger the permeabilization of mitochondrial membranes to initiate apoptosis or necrosis. Moreover, mitochondria have an important role in pro-inflammatory signaling. Autophagic turnover of cellular constituents, be it general or specific for mitochondria (mitophagy), eliminates dysfunctional or damaged mitochondria, thus counteracting degeneration, dampening inflammation, and preventing unwarranted cell loss. Decreased expression of genes that regulate autophagy or mitophagy can cause degenerative diseases in which deficient quality control results in inflammation and the death of cell populations. Thus, a combination of mitochondrial dysfunction and insufficient autophagy may contribute to multiple aging-associated pathologies.

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References and Notes

1
E. R. Mackenzie, B. Rakel, Eds., Complementary and Alternative Medicine for Older Adults: A Guide to Holistic Approaches to Healthy Aging (Springer, New York, 2006), p. 136.
2
Mattson M. P., Gleichmann M., Cheng A., Mitochondria in neuroplasticity and neurological disorders. Neuron 60, 748 (2008).
3
Gottlieb R. A., Mentzer R. M., Autophagy during cardiac stress: Joys and frustrations of autophagy. Annu. Rev. Physiol. 72, 45 (2010).
4
Hotchkiss R. S., Strasser A., McDunn J. E., Swanson P. E., Cell death. N. Engl. J. Med. 361, 1570 (2009).
5
Wallace D. C., Fan W., Procaccio V., Mitochondrial energetics and therapeutics. Annu. Rev. Pathol. 5, 297 (2010).
6
Tait S. W., Green D. R., Mitochondria and cell death: Outer membrane permeabilization and beyond. Nat. Rev. Mol. Cell Biol. 11, 621 (2010).
7
He C., Klionsky D. J., Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 43, 67 (2009).
8
Kroemer G., Mariño G., Levine B., Autophagy and the integrated stress response. Mol. Cell 40, 280 (2010).
9
Madeo F., Tavernarakis N., Kroemer G., Can autophagy promote longevity? Nat. Cell Biol. 12, 842 (2010).
10
Perry V. H., Cunningham C., Holmes C., Systemic infections and inflammation affect chronic neurodegeneration. Nat. Rev. Immunol. 7, 161 (2007).
11
Nakahira K., et al., Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 12, 222 (2011).
12
Kono H., Rock K. L., How dying cells alert the immune system to danger. Nat. Rev. Immunol. 8, 279 (2008).
13
Saitoh T., Akira S., Regulation of innate immune responses by autophagy-related proteins. J. Cell Biol. 189, 925 (2010).
14
Singh S. B., et al., Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria. Nat. Cell Biol. 12, 1154 (2010).
15
Zhou R., Yazdi A. S., Menu P., Tschopp J., A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221 (2011).
16
Kroemer G., Galluzzi L., Brenner C., Mitochondrial membrane permeabilization in cell death. Physiol. Rev. 87, 99 (2007).
17
Hailey D. W., et al., Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141, 656 (2010).
18
Carreira R. S., Lee Y., Ghochani M., Gustafsson A. B., Gottlieb R. A., Cyclophilin D is required for mitochondrial removal by autophagy in cardiac cells. Autophagy 6, 462 (2010).
19
Novak I., et al., Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 11, 45 (2010).
20
Sandoval H., et al., Essential role for Nix in autophagic maturation of erythroid cells. Nature 454, 232 (2008).
21
Youle R. J., Narendra D. P., Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol. 12, 9 (2011).
22
Chen D., et al., Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. J. Biol. Chem. 285, 38214 (2010).
23
Geisler S., et al., PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol. 12, 119 (2010).
24
Tanaka A., et al., Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J. Cell Biol. 191, 1367 (2010).
25
Michiorri S., et al., The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy. Cell Death Differ. 17, 962 (2010).
26
Lee J. Y., Nagano Y., Taylor J. P., Lim K. L., Yao T. P., Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J. Cell Biol. 189, 671 (2010).
27
Egan D. F., et al., Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331, 456 (2011).
28
Radoshevich L., et al., ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell 142, 590 (2010).
29
Levine B., Kroemer G., Autophagy in the pathogenesis of disease. Cell 132, 27 (2008).
30
Colell A., et al., GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 129, 983 (2007).
31
Xue L., Fletcher G. C., Tolkovsky A. M., Mitochondria are selectively eliminated from eukaryotic cells after blockade of caspases during apoptosis. Curr. Biol. 11, 361 (2001).
32
Tait S. W., et al., Resistance to caspase-independent cell death requires persistence of intact mitochondria. Dev. Cell 18, 802 (2010).
33
Korolchuk V. I., Mansilla A., Menzies F. M., Rubinsztein D. C., Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol. Cell 33, 517 (2009).
34
Lipinski M. M., et al., A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions. Dev. Cell 18, 1041 (2010).
35
Lipinski M. M., et al., Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc. Natl. Acad. Sci. U.S.A. 107, 14164 (2010).
36
Winslow A. R., et al., α-Synuclein impairs macroautophagy: Implications for Parkinson’s disease. J. Cell Biol. 190, 1023 (2010).
37
Bossy-Wetzel E., Petrilli A., Knott A. B., Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci. 31, 609 (2008).
38
Zheng S., et al., Deletion of the huntingtin polyglutamine stretch enhances neuronal autophagy and longevity in mice. PLoS Genet. 6, e1000838 (2010).
39
Martinez-Vicente M., et al., Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease. Nat. Neurosci. 13, 567 (2010).
40
Lee J. H., et al., Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141, 1146 (2010).
41
Moreau K., Luo S., Rubinsztein D. C., Cytoprotective roles for autophagy. Curr. Opin. Cell Biol. 22, 206 (2010).
42
Acín-Pérez R., Fernández-Silva P., Peleato M. L., Pérez-Martos A., Enriquez J. A., Respiratory active mitochondrial supercomplexes. Mol. Cell 32, 529 (2008).
43
Takeda K., et al., Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast. Proc. Natl. Acad. Sci. U.S.A. 107, 3540 (2010).
44
Renna M., Jimenez-Sanchez M., Sarkar S., Rubinsztein D. C., Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases. J. Biol. Chem. 285, 11061 (2010).
45
Rose C., et al., Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington’s disease. Hum. Mol. Genet. 19, 2144 (2010).
46
Sarkar S., et al., Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat. Chem. Biol. 3, 331 (2007).
47
Kinnally K. W., Peixoto P. M., Ryu S. Y., Dejean L. M., Is mPTP the gatekeeper for necrosis, apoptosis, or both? Biochim. Biophys. Acta 1813, 616 (2011).
48
Marzo I., et al., Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281, 2027 (1998).
49
Rostovtseva T. K., et al., Bid, but not Bax, regulates VDAC channels. J. Biol. Chem. 279, 13575 (2004).
50
Shimizu S., Narita M., Tsujimoto Y., Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 399, 483 (1999).
51
Baines C. P., et al., Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434, 658 (2005).
52
Nakagawa T., et al., Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434, 652 (2005).
53
Schinzel A. C., et al., Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc. Natl. Acad. Sci. U.S.A. 102, 12005 (2005).
54
Baines C. P., Kaiser R. A., Sheiko T., Craigen W. J., Molkentin J. D., Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat. Cell Biol. 9, 550 (2007).
55
Kokoszka J. E., et al., The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427, 461 (2004).
56
Kim I., Rodriguez-Enriquez S., Lemasters J. J., Selective degradation of mitochondria by mitophagy. Arch. Biochem. Biophys. 462, 245 (2007).
57
Rodriguez-Enriquez S., Kim I., Currin R. T., Lemasters J. J., Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy 2, 39 (2006).
58
Elmore S. P., Qian T., Grissom S. F., Lemasters J. J., The mitochondrial permeability transition initiates autophagy in rat hepatocytes. FASEB J. 15, 2286 (2001).
59
Teckman J. H., An J. K., Blomenkamp K., Schmidt B., Perlmutter D., Mitochondrial autophagy and injury in the liver in alpha 1-antitrypsin deficiency. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G851 (2004).
60
Rodríguez-Hernández A., et al., Coenzyme Q deficiency triggers mitochondria degradation by mitophagy. Autophagy 5, 19 (2009).
61
Kang H. T., Hwang E. S., Nicotinamide enhances mitochondria quality through autophagy activation in human cells. Aging Cell 8, 426 (2009).
62
Yang Y., Xing D., Zhou F., Chen Q., Mitochondrial autophagy protects against heat shock-induced apoptosis through reducing cytosolic cytochrome c release and downstream caspase-3 activation. Biochem. Biophys. Res. Commun. 395, 190 (2010).
63
Bani D., Filipponi F., Magnani L., Houssin D., Romagnoli P., Morphological changes in rat pancreatic acinar cells induced by long-term treatment with cyclosporine and their reversal after withdrawal. Transplantation 50, 830 (1990).
64
Pallet N., et al., Autophagy protects renal tubular cells against cyclosporine toxicity. Autophagy 4, 783 (2008).
65
Grumati P., et al., Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nat. Med. 16, 1313 (2010).
66
Willis S. N., Adams J. M., Life in the balance: how BH3-only proteins induce apoptosis. Curr. Opin. Cell Biol. 17, 617 (2005).
67
Youle R. J., Strasser A., The BCL-2 protein family: Opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 9, 47 (2008).
68
Rong Y., Distelhorst C. W., Bcl-2 protein family members: Versatile regulators of calcium signaling in cell survival and apoptosis. Annu. Rev. Physiol. 70, 73 (2008).
69
Pattingre S., et al., Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122, 927 (2005).
70
Erlich S., et al., Differential interactions between Beclin 1 and Bcl-2 family members. Autophagy 3, 561 (2007).
71
Feng W., Huang S., Wu H., Zhang M., Molecular basis of Bcl-xL’s target recognition versatility revealed by the structure of Bcl-xL in complex with the BH3 domain of Beclin-1. J. Mol. Biol. 372, 223 (2007).
72
Maiuri M. C., et al., Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J. 26, 2527 (2007).
73
Oberstein A., Jeffrey P. D., Shi Y., Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. J. Biol. Chem. 282, 13123 (2007).
74
Maiuri M. C., et al., BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L). Autophagy 3, 374 (2007).
75
Hamacher-Brady A., et al., Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ. 14, 146 (2007).
76
Rikka S., et al., Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover. Cell Death Differ. 18, 721 (2011).
77
Schweers R. L., et al., NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc. Natl. Acad. Sci. U.S.A. 104, 19500 (2007).
78
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 5, 720 (2009).
79
Lian J., et al., A natural BH3 mimetic induces autophagy in apoptosis-resistant prostate cancer via modulating Bcl-2-Beclin1 interaction at endoplasmic reticulum. Cell Death Differ. 18, 60 (2011).
80
McCoy F., et al., Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK. Cell Death Dis 1, e108 (2010).
81
Bellot G., et al., Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol. Cell. Biol. 29, 2570 (2009).
82
Chen G., et al., Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins. J. Biol. Chem. 274, 7 (1999).
83
Ray R., et al., BNIP3 heterodimerizes with Bcl-2/Bcl-X(L) and induces cell death independent of a Bcl-2 homology 3 (BH3) domain at both mitochondrial and nonmitochondrial sites. J. Biol. Chem. 275, 1439 (2000).
84
Schwarten M., et al., Nix directly binds to GABARAP: A possible crosstalk between apoptosis and autophagy. Autophagy 5, 690 (2009).
85
Ding W. X., et al., Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J. Biol. Chem. 285, 27879 (2010).
86
Vande Velde C., et al., BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore. Mol. Cell. Biol. 20, 5454 (2000).
87
Quinsay M. N., Thomas R. L., Lee Y., Gustafsson A. B., Bnip3-mediated mitochondrial autophagy is independent of the mitochondrial permeability transition pore. Autophagy 6, 855 (2010).
88
Ciechomska I. A., Goemans G. C., Skepper J. N., Tolkovsky A. M., Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function. Oncogene 28, 2128 (2009).
89
Mizushima N., Levine B., Cuervo A. M., Klionsky D. J., Autophagy fights disease through cellular self-digestion. Nature 451, 1069 (2008).
90
Vellai T., Takács-Vellai K., Sass M., Klionsky D. J., The regulation of aging: Does autophagy underlie longevity? Trends Cell Biol. 19, 487 (2009).
91
Bishop N. A., Lu T., Yankner B. A., Neural mechanisms of ageing and cognitive decline. Nature 464, 529 (2010).
92
Caramés B., Taniguchi N., Otsuki S., Blanco F. J., Lotz M., Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum. 62, 791 (2010).
93
Shibata M., et al., Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J. Biol. Chem. 281, 14474 (2006).
94
Keller J. N., et al., Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. Int. J. Biochem. Cell Biol. 36, 2376 (2004).
95
Crane J. D., Devries M. C., Safdar A., Hamadeh M. J., Tarnopolsky M. A., The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure. J. Gerontol. A Biol. Sci. Med. Sci. 65, 119 (2010).
96
Yoon Y. S., et al., Formation of elongated giant mitochondria in DFO-induced cellular senescence: involvement of enhanced fusion process through modulation of Fis1. J. Cell. Physiol. 209, 468 (2006).
97
Lee S., et al., Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence. J. Biol. Chem. 282, 22977 (2007).
98
Tandler B., Hoppel C. L., Studies on giant mitochondria. Ann. N. Y. Acad. Sci. 488, (1 Membrane Path), 65 (1986).
99
Coleman R., Silbermann M., Gershon D., Reznick A. Z., Giant mitochondria in the myocardium of aging and endurance-trained mice. Gerontology 33, 34 (1987).
100
Chan D. C., Mitochondria: Dynamic organelles in disease, aging, and development. Cell 125, 1241 (2006).
101
Liang X. H., et al., Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672 (1999).
102
Qu X., et al., Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 112, 1809 (2003).
103
Yue Z., Jin S., Yang C., Levine A. J., Heintz N., Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. U.S.A. 100, 15077 (2003).
104
Mathew R., et al., Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 21, 1367 (2007).
105
Karantza-Wadsworth V., et al., Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 21, 1621 (2007).
106
Mathew R., et al., Autophagy suppresses tumorigenesis through elimination of p62. Cell 137, 1062 (2009).
107
Cesari R., et al., Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc. Natl. Acad. Sci. U.S.A. 100, 5956 (2003).
108
Poulogiannis G., et al., PARK2 deletions occur frequently in sporadic colorectal cancer and accelerate adenoma development in Apc mutant mice. Proc. Natl. Acad. Sci. U.S.A. 107, 15145 (2010).
109
Wang F., et al., Parkin gene alterations in hepatocellular carcinoma. Genes Chromosomes Cancer 40, 85 (2004).
110
Veeriah S., et al., Somatic mutations of the Parkinson’s disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat. Genet. 42, 77 (2010).
111
Denison S. R., et al., Alterations in the common fragile site gene Parkin in ovarian and other cancers. Oncogene 22, 8370 (2003).
112
Picchio M. C., et al., Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin. Cancer Res. 10, 2720 (2004).
113
Cadwell K., et al., A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456, 259 (2008).
114
Komatsu M., et al., Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149 (2007).
115
Alvers A. L., et al., Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae. Aging Cell 8, 353 (2009).
116
Bjedov I., et al., Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 11, 35 (2010).
117
Harrison D. E., et al., Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392 (2009).
118
Morselli E., et al., Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis 1, e10 (2010).
119
Eisenberg T., et al., Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 11, 1305 (2009).
120
Meléndez A., et al., Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387 (2003).
121
Jia K., Levine B., Autophagy is required for dietary restriction-mediated life span extension in C. elegans. Autophagy 3, 597 (2007).
122
Simonsen A., et al., Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4, 176 (2008).
123
Zhang C., Cuervo A. M., Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat. Med. 14, 959 (2008).
124
Morselli E., et al., Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J. Cell Biol. 192, 615 (2011).
125
Jaeger P. A., et al., Regulation of amyloid precursor protein processing by the Beclin 1 complex. PLoS ONE 5, e11102 (2010).
126
Perez M., et al., Tau—an inhibitor of deacetylase HDAC6 function. J. Neurochem. 109, 1756 (2009).
127
Pickford F., et al., The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J. Clin. Invest. 118, 2190 (2008).
128
Rhein V., et al., Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice. Proc. Natl. Acad. Sci. U.S.A. 106, 20057 (2009).
129
Wang X., et al., Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J. Neurosci. 29, 9090 (2009).
130
Area-Gomez E., et al., Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Am. J. Pathol. 175, 1810 (2009).
131
Metzger S., et al., Age at onset in Huntington’s disease is modified by the autophagy pathway: Implication of the V471A polymorphism in Atg7. Hum. Genet. 128, 453 (2010).
132
Thoreen C. C., Sabatini D. M., Huntingtin aggregates ask to be eaten. Nat. Genet. 36, 553 (2004).
133
Ayala A., Venero J. L., Cano J., Machado A., Mitochondrial toxins and neurodegenerative diseases. Front. Biosci. 12, 986 (2007).
134
Thomas K. J., et al., DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Hum. Mol. Genet. 20, 40 (2011).
135
González-Polo R., et al., Silencing DJ-1 reveals its contribution in paraquat-induced autophagy. J. Neurochem. 109, 889 (2009).
136
Kim Y., et al., PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem. Biophys. Res. Commun. 377, 975 (2008).

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Volume 333 | Issue 6046
26 August 2011

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Acknowledgments

Acknowledgments: We apologize to all colleagues whose work we could not cite owing to space limitations. D.R.G. receives grants from the NIH and from the American Lebanese Syrian Associated Charities. L.G. is financed by the European Union (EU) (APO-SYS). G.K. is supported by Agence Nationale de la Recherche, Association pour la Recherche sur le Cancer, AXA Chair for Longevity Research, Fondation pour la Recherche Médicale, Institut National du Cancer, EU, and Ligue Nationale Contre le Cancer (équipe labelisée).

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Douglas R. Green* [email protected]
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
Lorenzo Galluzzi
INSERM, U848, F-94805 Villejuif, France.
Institut Gustave Roussy, F-94805 Villejuif, France.
Université Paris-Sud, Paris 11, F-94805 Villejuif, France.
Guido Kroemer* [email protected]
INSERM, U848, F-94805 Villejuif, France.
Metabolomics Platform, Institut Gustave Roussy, F-94805 Villejuif, France.
Centre de Recherche des Cordeliers, F-75005 Paris, France.
Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique–Hôpitaux de Paris, F-75908 Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, F-75270 Paris, France.

Notes

*
To whom correspondence should be addressed. E-mail: [email protected] (D.R.G.); [email protected] (G.K.)

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