Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice.
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.
Komatsu
Masaaki
M
Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.
Waguri
Satoshi
S
Ueno
Takashi
T
Iwata
Junichi
J
Murata
Shigeo
S
Tanida
Isei
I
Ezaki
Junji
J
Mizushima
Noboru
N
Ohsumi
Yoshinori
Y
Uchiyama
Yasuo
Y
Kominami
Eiki
E
Tanaka
Keiji
K
Chiba
Tomoki
T
D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy / Q000235:genetics*; D000071193:Autophagy-Related Protein 7; D002460:Cell Line; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006529:Hepatomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007425:Intracellular Membranes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008099:Liver / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015388:Organelles / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D010641:Phenotype; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013217:Starvation / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
C114830:ATG7 protein, S cerevisiae; C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D000071193:Autophagy-Related Protein 7