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Science 5 November 2004:
Vol. 306. no. 5698, pp. 990 - 995
DOI: 10.1126/science.1099993
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Review

Autophagy in Health and Disease: A Double-Edged Sword

Takahiro Shintani and Daniel J. Klionsky*

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.

University of Michigan, Life Sciences Institute, and Departments of Molecular, Cellular, and Developmental Biology and of Biological Chemistry, Ann Arbor, MI 48109–2216, USA.

* To whom correspondence should be addressed. E-mail: klionsky{at}umich.edu

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Functional Analysis of the ATG8 Homologue Aoatg8 and Role of Autophagy in Differentiation and Germination in Aspergillus oryzae..
T. Kikuma, M. Ohneda, M. Arioka, and K. Kitamoto (2006)
Eukaryot. Cell 5, 1328-1336
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Autophagy in Innate Immunity against Intracellular Bacteria.
A. Amano, I. Nakagawa, and T. Yoshimori (2006)
J. Biochem. 140, 161-166
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Disruption of Autophagy at the Maturation Step by the Carcinogen Lindane Is Associated with the Sustained Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Activity..
E. Corcelle, M. Nebout, S. Bekri, N. Gauthier, P. Hofman, P. Poujeol, P. Fenichel, and B. Mograbi (2006)
Cancer Res. 66, 6861-6870
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Molecular pathogenesis of spinocerebellar ataxias.
A. M. Duenas, R. Goold, and P. Giunti (2006)
Brain 129, 1357-1370
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Regulation of Intracellular Accumulation of Mutant Huntingtin by Beclin 1.
M. Shibata, T. Lu, T. Furuya, A. Degterev, N. Mizushima, T. Yoshimori, M. MacDonald, B. Yankner, and J. Yuan (2006)
J. Biol. Chem. 281, 14474-14485
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Aggresomes and autophagy generate sites for virus replication..
T. Wileman (2006)
Science 312, 875-878
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Autophagic cell death of malignant glioma cells induced by a conditionally replicating adenovirus..
H. Ito, H. Aoki, F. Kuhnel, Y. Kondo, S. Kubicka, T. Wirth, E. Iwado, A. Iwamaru, K. Fujiwara, K. R. Hess, et al. (2006)
J Natl Cancer Inst 98, 625-636
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Sialic acid binding immunoglobulin-like lectins may regulate innate immune responses by modulating the life span of granulocytes.
S. von Gunten and H.-U. Simon (2006)
FASEB J 20, 601-605
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Chemotherapeutic approaches for targeting cell death pathways..
M. S. Ricci and W.-X. Zong (2006)
Oncologist 11, 342-357
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Elongation factor-2 kinase regulates autophagy in human glioblastoma cells..
H. Wu, J.-M. Yang, S. Jin, H. Zhang, and W. N. Hait (2006)
Cancer Res. 66, 3015-3023
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