Self-eating and self-killing: Crosstalk between autophagy and apoptosis

Nature Reviews Molecular Cell Biology

Volumn 8, Issue 9, 2007, Pages 741-752

  Maiuri, M Chiara ^a,b,c   Zalckvar, Einat ^d   Kimchi, Adi ^d   Kroemer, Guido ^a,b,e  

^a Institut Gustave Roussy   (France)

^b INSTITUT GUSTAVE ROUSSY   (France)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^d WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^e UNIVERSITÉ PARIS SACLAY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

APOPTOSIS INDUCING FACTOR; APOPTOSOME; BH3 PROTEIN; CASPASE; CATHEPSIN; CYTOCHROME C; DEATH ASSOCIATED PROTEIN KINASE; DEATH RECEPTOR; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN P53; REACTIVE OXYGEN METABOLITE;

APOPTOSIS; AUTOPHAGY; CELL CYCLE; CELL CYCLE ARREST; CELL DEATH; CELL ORGANELLE; CELL PROTECTION; CELLULAR STRESS RESPONSE; GENOME; HUMAN; LYSOSOME MEMBRANE; POLARIZATION; PRIORITY JOURNAL; PROTEIN AGGREGATION; REVIEW; TUMOR SUPPRESSOR GENE;

ANIMALS; APOPTOSIS; AUTOPHAGY; CELL CYCLE; HUMANS; SIGNAL TRANSDUCTION;

EID: 34548188741     PISSN: 14710072     EISSN: 14710080     Source Type: Journal    
DOI: 10.1038/nrm2239     Document Type: Review

References (99)

1. Danial, N. N. & Korsmeyer, S. J. Cell death: critical control points. Cell 116, 205-219 (2004).
2. Green, D. R. Apoptotic pathways: ten minutes to dead. Cell 121, 671-674 (2005).
3. Kroemer, G. et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 12 (Suppl. 2), 1463-1467 (2005).
4. Shintani, T. & Klionsky, D. J. Autophagy in health and disease: a double-edged sword. Science 306, 990-995 (2004).
5. Rubinsztein, D. C., Gestwicki, J. E., Murphy, L. O. & Klionsky, D. J. Potential therapeutic applications of autophagy. Nature Rev. Drug Discov. 6, 304-312 (2007). A landmark review that enumerates the potential therapeutic possibilities of autophagy inhibition and stimulation.
6. Lum, J. J., DeBerardinis, R. J. & Thompson, C. B. Autophagy in metazoans: cell survival in the land of plenty. Nature Rev. Mol. Cell Biol. 6, 439-448 (2005).
7. Baehrecke, E. H. Autophagy: dual roles in life and death? Nature Rev. Mol. Cell Biol. 6, 505-510 (2005).
8. Levine, B. & Yuan, J. Autophagy in cell death: an innocent convict? J. Clin. Invest. 115, 2679-2688 (2005).
9. Kroemer, G. & Jaattela, M. Lysosomes and autophagy in cell death control. Nature Rev. Cancer 5, 886-897 (2005).
10. Kondo, Y., Kanzawa, T., Sawaya, R. & Kondo, S. The role of autophagy in cancer development and response to therapy. Nature Rev. Cancer 5, 726-734 (2005).
11. Gozuacik, D. & Kimchi, A. Autophagy and cell death. Curr. Top. Dev. Biol. 78, 217-245 (2007).
12. Lockshin, R. A. & Zakeri, Z. Programmed cell death and apoptosis: origins of the theory. Nature Rev. Mol. Cell Biol. 2, 545-550 (2001). A fascinating historical overview on the theory of developmental and homeostatic cell death.
13. Shimizu, S. et al. Role of Bcl-2 family proteins in a nonapoptotic programmed cell death dependent on autophagy genes. Nature Cell Biol. 6, 1221-1228 (2004).
14. Madden, D. T., Egger, L. & Bredesen, D. E. A calpain-like protease inhibits autophagic cell death. Autophagy 3, 519-522 (2007).
15. Xu, Y., Kim, S. O., Li, Y. & Han, J. Autophagy contributes to caspase-independent macrophage cell death. J. Biol. Chem. 281, 19179-19187 (2006).
16. Yu, L. et al. Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304, 1500-1502 (2004).
17. Yu, L. et al. Autophagic programmed cell death by selective catalase degradation. Proc. Natl Acad. Sci. USA 103, 4952-4957 (2006). Provides the first example of how selective degradation of a vital cellular protein by autophagy can precipitate cell death.
18. Lum, J. J. et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120, 237-248 (2005). Reports the discovery of a close link between autophagy, cellular atrophy and the absence of growth-factor signalling in which autophagy allows cells to adapt to a failing supply of metabolites.
19. Gonzalez-Polo, R. A. et al. The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J. Cell Sci. 118, 3091-3102 (2005).
20. Boya, P. et al. Inhibition of macroautophagy triggers apoptosis. Mol. Cell Biol. 25, 1025-1040 (2005). The first report showing that autophagy avoids apoptosis in the context of growth-factor and nutrient depletion.
21. Hara, T. et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885-889 (2006).
22. Komatsu, M. et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880-884 (2006).
23. Pua, H. H., Dzhagalov, I., Chuck, M., Mizushima, N. & He, Y. W. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J. Exp. Med. 204, 25-31 (2007).
24. Takacs-Vellai, K. et al. Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans. Curr. Biol. 15, 1513-1517 (2005).
25. Nutt, L. K. et al. Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Cell 123, 89-103 (2005).
26. Kroemer, G., Galluzzi, L. & Brenner, C. Mitochondrial membrane permeabilization in cell death. Physiol. Rev. 87, 99-163 (2007).
27. Golstein, P. & Kroemer, G. Cell death by necrosis: towards a molecular definition. Trends Biochem. Sci. 32, 37-43 (2007).
28. Katayama, M., Kawaguchi, T., Berger, M. S. & Pieper, R. O. DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ. 14, 548-558 (2007).
29. Degenhardt, K. et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10, 51-64 (2006). A fascinating study of the potential role of autophagy in the growth of cancer cells in vivo.
30. Williams, A. et al. Aggregate-prone proteins are cleared from the cytosol by autophagy: therapeutic implications. Curr. Top. Dev. Biol. 76, 89-101 (2006).
31. Ravikumar, B. et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nature Genet. 36, 585-595 (2004). The first report to show that pharmacological stimulation of autophagy may reduce the histopathological and clinical signs of neurodegeneration in vivo.
32. Sarkar, S. et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J. Cell Biol. 170, 1101-1111 (2005).
33. Shibata, M. et al. Regulation of intracellular accumulation of mutant huntingtin by beclin 1. J. Biol. Chem. 281, 14474-14485 (2006).
34. Cuervo, A. M. Autophagy in neurons: it is not all about food. Trends Mol. Med. 12, 461-464 (2006).
35. Ravikumar, B., Berger, Z., Vacher, C., O'Kane, C. J. & Rubinsztein, D. C. Rapamycin pre-treatment protects against apoptosis. Hum. Mol. Genet. 15, 1209-1216 (2006).
36. Colell, A. et al. GAPDH and autophagy preserve cellular survival during caspase-independent cell death. Cell 129, 983-997 (2007). A highly intriguing report suggesting that GAPDH can stimulate autophagy by its action as a nuclear transcription factor, and thereby facilitates the survival of cells that have undergone MOMP.
37. Liang, J. et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nature Cell Biol. 9, 218-224 (2007).
38. Clarke, P. G. Developmental cell death: morphological diversity and multiple mechanisms. Anat. Embryol. (Berl.) 181, 195-213 (1990).
39. Martin, D. N. & Baehrecke, E. H. Caspases function in autophagic programmed cell death in Drosophila. Development 131, 275-284 (2004).
40. Scott, R. C., Juhasz, G. & Neufeld, T. P. Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr. Biol. 17, 1-11 (2007). Reports an in vivo experiment that shows how autophagy can indirectly trigger cell death through the induction of apoptosis.
41. Espert, L. et al. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J. Clin. Invest. 116, 2161-2172 (2006).
42. 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. USA 100, 15077-15082 (2003).
43. Qu, X. et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 112, 1809-1820 (2003).
44. Mathew, R. et al. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 21, 1367-1381 (2007). This excellent paper suggests a mechanistic explanation for the tumour-suppressive function of beclin-1, which is required for genomic stability.
45. Scherz-Shouval, R. et al. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 26, 1749-1760 (2007).
46. Lavieu, G. et al. Regulation of autophagy by sphingosine kinase 1 and its role in cell survival during nutrient starvation. J. Biol. Chem. 281, 8518-8527 (2006).
47. Hait, N. C., Oskeritzian, C. A., Paugh, S. W., Milstien, S. & Spiegel, S. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim. Biophys. Acta 1758, 2016-2026 (2006).
48. 2+: molecular determinants and functional consequences. Physiol. Rev. 86, 369-408 (2006).
49. Hoyer-Hansen, M. et al. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-β, and Bcl-2. Mol. Cell 25, 193-205 (2007).
50. Demarchi, F. et al. Calpain is required for macroautophagy in mammalian cells. J. Cell Biol. 175, 595-605 (2006).
51. Yousefi, S. et al. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nature Cell Biol. 8, 1124-1132 (2006). An intriguing report that documents how ATG5 protein can switch from its normal function in autophagy to a pro-apoptotic one.
52. Vousden, K. H. & Lane, D. P. p53 in health and disease. Nature Rev. Mol. Cell Biol. 8, 275-283 (2007).
53. Zeng, X., Yan, T., Schupp, J. E., Seo, Y. & Kinsella, T. J. DNA mismatch repair initiates 6-thioguanine-induced autophagy through p53 activation in human tumor cells. Clin. Cancer Res. 13, 1315-1321 (2007).
54. Feng, Z., Zhang, H., Levine, A. J. & Jin, S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl Acad. Sci. USA 102, 8204-8209 (2005).
55. Crighton, D. et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 126, 121-134 (2006).
56. Galonek, H. L. & Hardwick, J. M. Upgrading the BCL-2 network. Nature Cell Biol. 8, 1317-1319 (2006).
57. Adams, J. M. & Cory, S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26, 1324-1337 (2007).
58. L and a BH3-like domain in Beclin-1. EMBO J. 26, 2527-2539 (2007). This paper explains the triangular relationship between the essential autophagy protein beclin-1, the anti-apoptotic multidomain proteins of the BCL2 family and BH3-only proteins.
59. Kessel, D. & Reiners, J. J. Jr. Initiation of apoptosis and autophagy by the Bcl-2 antagonist HA14-1. Cancer Lett. 249, 294-299 (2007).
60. Daido, S. et al. Pivotal role of the cell death factor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells. Cancer Res. 64, 4286-4293 (2004).
61. Hamacher-Brady, A. et al. Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ. 14, 146-157 (2007).
62. L-beclin 1 peptide complex: beclin 1 is a novel BH3-only protein. J. Biol. Chem. 282, 13123-13132 (2007).
63. L. Autophagy 3, 374-376 (2007).
64. Nobukuni, T., Kozma, S. C. & Thomas, G. hvps34, an ancient player, enters a growing game: mTOR complex1/S6K1 signaling. Curr. Opin. Cell Biol. 19, 135-141 (2007).
65. Bialik, S. & Kimchi, A. The death-associated protein kinases: structure, function, and beyond. Annu. Rev. Biochem. 75, 189-210 (2006).
66. Raveh, T., Droguett, G., Horwitz, M. S., DePinho, R. A. & Kimchi, A. DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation. Nature Cell Biol. 3, 1-7 (2001).
67. Wang, W. J., Kuo, J. C., Yao, C. C. & Chen, R. H. DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals. J. Cell Biol. 159, 169-179 (2002).
68. Jang, C. W. et al. TGF-β induces apoptosis through Smad-mediated expression of DAP-kinase. Nature Cell Biol. 4, 51-58 (2002).
69. Inbal, B., Bialik, S., Sabanay, I., Shani, G. & Kimchi, A. DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J. Cell Biol. 157, 455-468 (2002).
70. Shani, G. et al. Death-associated protein kinase phosphorylates ZIP kinase, forming a unique kinase hierarchy to activate its cell death functions. Mol. Cell Biol. 24, 8611-8626 (2004).
71. Raval, A. et al. Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell 129, 879-890 (2007)
72. Reef, S. et al. A short mitochondrial form of p19ARF induces autophagy and caspase-independent cell death. Mol. Cell 22, 463-475 (2006). Demonstrates that a short isoform of the ARF protein (generated by internal initiation of translation) can induce autophagy, presumably through an action on depolarized but not permeabilized mitochondria.
73. Rodriguez-Enriquez, S., Kim, I., Currin, R. T. & Lemasters, J. J. Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy 2, 39-46 (2006).
74. Vande Velde, C. et al. BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore. Mol. Cell Biol. 20, 5454-5468 (2000).
75. Zhu, J. H. et al. Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4-phenylpyridinium-induced cell death. Am. J. Pathol. 170, 75-86 (2007).
76. Xu, C., Bailly-Maitre, B. & Reed, J. C. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest. 115, 2656-2664 (2005).
77. Yorimitsu, T., Nair, U., Yang, Z. & Klionsky, D. J. Endoplasmic reticulum stress triggers autophagy. J. Biol. Chem. 281, 30299-30304 (2006).
78. Schroder, M. & Kaufman, R. J. The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739-789 (2005).
79. Criollo, A. et al. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 14, 1029-1039 (2007).
80. Hetz, C. et al. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1α. Science 312, 572-576 (2006).
81. Boya, P., Cohen, I., Zamzami, N., Vieira, H. L. & Kroemer, G. Endoplasmic reticulum stress-induced cell death requires mitochondrial membrane permeabilization. Cell Death Differ. 9, 465-467 (2002).
82. Ogata, M. et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol. Cell Biol. 26, 9220-9231 (2006). Shows for the first time that ER stress can stimulate autophagy in mammalian cells.
83. Kouroku, Y. et al. ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamineinduced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 14, 230-239 (2007).
84. Ding, W. X. et al. Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J. Biol. Chem. (2006).
85. Pyo, J. O. et al. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J. Biol. Chem. 280, 20722-20729 (2005).
86. Liang, C. et al. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nature Cell Biol. 8, 688-699 (2006).
87. Fimia, G. M. et al. Ambra1 regulates autophagy and development of the nervous system. Nature 24 Jun 2007 (doi:10.1038/nature05925). References 85 and 87 report the identification of two beclin-1-binding proteins that are required for the induction of autophagy.
88. Pattingre, S. et al. Bcl-2 antiapoptotic proteins inhibit beclin 1-dependent autophagy. Cell 122, 927-939 (2005).
89. L, induces a caspase-independent autophagic cell death. Cell Death Differ. 10, 798-807 (2003).
90. Qu, X. et al. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128, 931-946 (2007). Indicates that, during developmental cell death, autophagy may be a mechanism that occurs before (but independently of) apoptosis and allows for optimal heterophagic removal of the dying cell.
91. Tanida, I., Ueno, T. & Kominami, E. LC3 conjugation system in mammalian autophagy. Int. J. Biochem. Cell Biol. 36, 2503-2518 (2004).
92. Levine, B. & Klionsky, D. J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463-477 (2004).
93. Krammer, P. H. CD95's deadly mission in the immune system. Nature 407, 789-795 (2000).
94. Tinel, A. et al. Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-κB pathway. EMBO J. 26, 197-208 (2007).
95. Kroemer, G. & Martin, S. J. Caspase-independent cell death. Nature Med. 11, 725-730 (2005).
96. Arama, E., Agapite, J. & Steller, H. Caspase activity and a specific cytochrome c are required for sperm differentiation in Drosophila. Dev. Cell 4, 687-697 (2003).
97. Kuranaga, E. & Miura, M. Nonapoptotic functions of caspases: caspases as regulatory molecules for immunity and cell-fate determination. Trends Cell Biol. 17, 135-144 (2007).
98. L regulates synaptic plasticity. Mol. Interv. 6, 208-222 (2006).
99. Zermati, Y. et al. Non-apoptotic role for Apaf-1 in the DNA damage response. Mol. Cell in the press.