Autophagy in Health and Disease: a Double-edged Sword

Overview

Journal Science

Specialty Science

Date 2004 Nov 6

PMID 15528435

Citations 1132

Authors

Takahiro Shintani

Daniel J Klionsky

Affiliations

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Abstract

Autophagy, the process by which cells recycle cytoplasm and dispose of excess or defective organelles, has entered the research spotlight largely owing to the discovery of the protein components that drive this process. Identifying the autophagy genes in yeast and finding orthologs in other organisms reveals the conservation of the mechanism of autophagy in eukaryotes and allows the use of molecular genetics and biology in different model systems to study this process. By mostly morphological studies, autophagy has been linked to disease processes. Whether autophagy protects from or causes disease is unclear. Here, we summarize current knowledge about the role of autophagy in disease and health.

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References

Diaz-Hernandez M, Hernandez F, Martin-Aparicio E, Gomez-Ramos P, Moran M, Castano J . Neuronal induction of the immunoproteasome in Huntington's disease. J Neurosci. 2003; 23(37):11653-61. PMC: 6740941. View

Rich K, Burkett C, Webster P . Cytoplasmic bacteria can be targets for autophagy. Cell Microbiol. 2003; 5(7):455-68. DOI: 10.1046/j.1462-5822.2003.00292.x. View

Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A . Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003; 112(12):1809-20. PMC: 297002. DOI: 10.1172/JCI20039. View

Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T . Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature. 2000; 406(6798):906-10. DOI: 10.1038/35022604. View

Stefanis L, Larsen K, Rideout H, Sulzer D, Greene L . Expression of A53T mutant but not wild-type alpha-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J Neurosci. 2001; 21(24):9549-60. PMC: 6763041. View

Ravikumar B, Vacher C, Berger Z, Davies J, Luo S, Oroz L . Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet. 2004; 36(6):585-95. DOI: 10.1038/ng1362. View

Ravikumar B, Duden R, Rubinsztein D . Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet. 2002; 11(9):1107-17. DOI: 10.1093/hmg/11.9.1107. View

Suhy D, Giddings Jr T, Kirkegaard K . Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: an autophagy-like origin for virus-induced vesicles. J Virol. 2000; 74(19):8953-65. PMC: 102091. DOI: 10.1128/jvi.74.19.8953-8965.2000. View

Nakagawa I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H, Kamimoto T . Autophagy defends cells against invading group A Streptococcus. Science. 2004; 306(5698):1037-40. DOI: 10.1126/science.1103966. View

10.

Leib D, Machalek M, Williams B, Silverman R, Virgin H . Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene. Proc Natl Acad Sci U S A. 2000; 97(11):6097-101. PMC: 18564. DOI: 10.1073/pnas.100415697. View

11.

Melendez A, Talloczy Z, Seaman M, Eskelinen E, Hall D, Levine B . Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 2003; 301(5638):1387-91. DOI: 10.1126/science.1087782. View

12.

Sun X, Butterworth M, MacFarlane M, Dubiel W, Ciechanover A, Cohen G . Caspase activation inhibits proteasome function during apoptosis. Mol Cell. 2004; 14(1):81-93. DOI: 10.1016/s1097-2765(04)00156-x. View

13.

Lipinski M, Yuan J . Mechanisms of cell death in polyglutamine expansion diseases. Curr Opin Pharmacol. 2004; 4(1):85-90. DOI: 10.1016/j.coph.2003.09.008. View

14.

Yuan J, Lipinski M, Degterev A . Diversity in the mechanisms of neuronal cell death. Neuron. 2003; 40(2):401-13. DOI: 10.1016/s0896-6273(03)00601-9. View

15.

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

16.

Lee C, Baehrecke E . Steroid regulation of autophagic programmed cell death during development. Development. 2001; 128(8):1443-55. DOI: 10.1242/dev.128.8.1443. View

17.

Longo V, Finch C . Evolutionary medicine: from dwarf model systems to healthy centenarians?. Science. 2003; 299(5611):1342-6. DOI: 10.1126/science.1077991. View

18.

Scarlatti F, Bauvy C, Ventruti A, Sala G, Cluzeaud F, Vandewalle A . Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1. J Biol Chem. 2004; 279(18):18384-91. DOI: 10.1074/jbc.M313561200. View

19.

Gozuacik D, Kimchi A . Autophagy as a cell death and tumor suppressor mechanism. Oncogene. 2004; 23(16):2891-906. DOI: 10.1038/sj.onc.1207521. View

20.

Xue L, Fletcher G, Tolkovsky A . Mitochondria are selectively eliminated from eukaryotic cells after blockade of caspases during apoptosis. Curr Biol. 2001; 11(5):361-5. DOI: 10.1016/s0960-9822(01)00100-2. View