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PMID: 15866887 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 169 ·No. 3 ·2005-05-09 ·Pages 425-34

Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y, Kominami E, Tanaka K, Chiba T

Abstract

Autophagy is a membrane-trafficking mechanism that delivers cytoplasmic constituents into the lysosome/vacuole for bulk protein degradation. This mechanism is involved in the preservation of nutrients under starvation condition as well as the normal turnover of cytoplasmic component. Aberrant autophagy has been reported in several neurodegenerative disorders, hepatitis, and myopathies. Here, we generated conditional knockout mice of Atg7, an essential gene for autophagy in yeast. Atg7 was essential for ATG conjugation systems and autophagosome formation, amino acid supply in neonates, and starvation-induced bulk degradation of proteins and organelles in mice. Furthermore, Atg7 deficiency led to multiple cellular abnormalities, such as appearance of concentric membranous structure and deformed mitochondria, and accumulation of ubiquitin-positive aggregates. Our results indicate the important role of autophagy in starvation response and the quality control of proteins and organelles in quiescent cells.

MeSH Terms
Animals Animals, Newborn Autophagy/genetics Autophagy-Related Protein 7 Cell Line Hepatocytes/metabolism,pathology,ultrastructure Hepatomegaly/metabolism,pathology,physiopathology Inclusion Bodies/metabolism,pathology,ultrastructure Intracellular Membranes/metabolism,pathology,ultrastructure Liver/abnormalities,metabolism,pathology Mice Mice, Knockout Microtubule-Associated Proteins/genetics Mitochondria/metabolism,pathology,ultrastructure Organelles/metabolism,pathology,ultrastructure Phenotype Saccharomyces cerevisiae Proteins/genetics Starvation/metabolism Ubiquitin/metabolism
Chemicals
ATG7 protein, S cerevisiae Atg7 protein, mouse Microtubule-Associated Proteins Saccharomyces cerevisiae Proteins Ubiquitin Autophagy-Related Protein 7
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Komatsu Masaaki
Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.
Waguri Satoshi
Ueno Takashi
Iwata Junichi
Murata Shigeo
Tanida Isei
Ezaki Junji
Mizushima Noboru
Ohsumi Yoshinori
Uchiyama Yasuo
Kominami Eiki
Tanaka Keiji
Chiba Tomoki
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200412022
Published
2005-05-09
Epub
2005-00-02
Pages
425-34
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171928
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200412022 PMC Full Text View journal details
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