Autophagic Cell Death: the Story of a Misnomer

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2008 Oct 31

PMID 18971948

Citations 717

Authors

Guido Kroemer

Beth Levine

Affiliations

Soon will be listed here.

Abstract

Dying cells often display a large-scale accumulation of autophagosomes and hence adopt a morphology called autophagic cell death. In many cases, it is agreed that this autophagic cell death is cell death with autophagy rather than cell death by autophagy. Here, we evaluate the accumulating body of literature that argues that cell death occurs by autophagy. We also list the caveats that must be considered when deciding whether or not autophagy is an important effector mechanism of cell death.

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References

Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson C . Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004; 6(12):1221-8. DOI: 10.1038/ncb1192. View

Berry D, Baehrecke E . Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell. 2007; 131(6):1137-48. PMC: 2180345. DOI: 10.1016/j.cell.2007.10.048. View

Berry D, Baehrecke E . Autophagy functions in programmed cell death. Autophagy. 2008; 4(3):359-60. PMC: 2782713. DOI: 10.4161/auto.5575. View

Codogno P, Meijer A . Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ. 2005; 12 Suppl 2:1509-18. DOI: 10.1038/sj.cdd.4401751. View

Shintani T, Klionsky D . Autophagy in health and disease: a double-edged sword. Science. 2004; 306(5698):990-5. PMC: 1705980. DOI: 10.1126/science.1099993. View

Akar U, Chaves-Reyez A, Barria M, Tari A, Sanguino A, Kondo Y . Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells. Autophagy. 2008; 4(5):669-79. DOI: 10.4161/auto.6083. View

Kroemer G, Jaattela M . Lysosomes and autophagy in cell death control. Nat Rev Cancer. 2005; 5(11):886-97. DOI: 10.1038/nrc1738. View

Degterev A, Hitomi J, Germscheid M, Chen I, Korkina O, Teng X . Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008; 4(5):313-21. PMC: 5434866. DOI: 10.1038/nchembio.83. View

Fimia G, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R . Ambra1 regulates autophagy and development of the nervous system. Nature. 2007; 447(7148):1121-5. DOI: 10.1038/nature05925. View

10.

Ding W, Ni H, Gao W, Hou Y, Melan M, Chen X . Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J Biol Chem. 2006; 282(7):4702-4710. DOI: 10.1074/jbc.M609267200. View

11.

Zong W, LINDSTEN T, Ross A, Macgregor G, Thompson C . BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 2001; 15(12):1481-6. PMC: 312722. DOI: 10.1101/gad.897601. View

12.

Perelman B, Dafni N, Naiman T, Eli D, Yaakov M, Feng T . Molecular cloning of a novel human gene encoding a 63-kDa protein and its sublocalization within the 11q13 locus. Genomics. 1997; 41(3):397-405. DOI: 10.1006/geno.1997.4623. View

13.

Reef S, Zalckvar E, Shifman O, Bialik S, Sabanay H, Oren M . A short mitochondrial form of p19ARF induces autophagy and caspase-independent cell death. Mol Cell. 2006; 22(4):463-75. DOI: 10.1016/j.molcel.2006.04.014. View

14.

Samara C, Syntichaki P, Tavernarakis N . Autophagy is required for necrotic cell death in Caenorhabditis elegans. Cell Death Differ. 2007; 15(1):105-12. DOI: 10.1038/sj.cdd.4402231. View

15.

Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin K . The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci U S A. 2007; 104(35):14050-5. PMC: 1955809. DOI: 10.1073/pnas.0704014104. View

16.

Wei M, Zong W, Cheng E, LINDSTEN T, Panoutsakopoulou V, Ross A . Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001; 292(5517):727-30. PMC: 3049805. DOI: 10.1126/science.1059108. View

17.

Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S . Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science. 2004; 304(5676):1500-2. DOI: 10.1126/science.1096645. View

18.

Tresse E, Kosta A, Luciani M, Golstein P . From autophagic to necrotic cell death in Dictyostelium. Semin Cancer Biol. 2006; 17(2):94-100. DOI: 10.1016/j.semcancer.2006.10.010. View

19.

Wyllie A, KERR J, Currie A . Cell death: the significance of apoptosis. Int Rev Cytol. 1980; 68:251-306. DOI: 10.1016/s0074-7696(08)62312-8. View

20.

Levine B, Kroemer G . Autophagy in the pathogenesis of disease. Cell. 2008; 132(1):27-42. PMC: 2696814. DOI: 10.1016/j.cell.2007.12.018. View