Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice

doi:10.1083/jcb.200412022

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Published online 2 May 2005. doi:10.1083/jcb.200412022
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 3, 425-434

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Article

Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice

Masaaki Komatsu¹^,3, Satoshi Waguri², Takashi Ueno³, Junichi Iwata³, Shigeo Murata¹, Isei Tanida³, Junji Ezaki³, Noboru Mizushima⁴, Yoshinori Ohsumi⁵, Yasuo Uchiyama², Eiki Kominami³, Keiji Tanaka¹, and Tomoki Chiba¹

¹ Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan
² Department of Cell Biology and Neurosciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
³ Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
⁴ Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan
⁵ Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan

Correspondence to Tomoki Chiba: tchiba{at}rinshoken.or.jp

Autophagy is a membrane-trafficking mechanism that deliverscytoplasmic constituents into the lysosome/vacuole for bulkprotein degradation. This mechanism is involved in the preservationof nutrients under starvation condition as well as the normalturnover of cytoplasmic component. Aberrant autophagy has beenreported in several neurodegenerative disorders, hepatitis,and myopathies. Here, we generated conditional knockout miceof Atg7, an essential gene for autophagy in yeast. Atg7 wasessential for ATG conjugation systems and autophagosome formation,amino acid supply in neonates, and starvation-induced bulk degradationof proteins and organelles in mice. Furthermore, Atg7 deficiencyled to multiple cellular abnormalities, such as appearance ofconcentric membranous structure and deformed mitochondria, andaccumulation of ubiquitin-positive aggregates. Our results indicatethe important role of autophagy in starvation response and thequality control of proteins and organelles in quiescent cells.

Abbreviations used in this paper: MEF, mouse embryonic fibroblast;pIpC, polyinosinic acid–polycytidylic acid; PNS, postnuclearsupernatant; SDH, succinate dehydrogenase.

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