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

• Published in: The Journal of cell biology Vol. 169; no. 3; pp. 425 - 434
• Main Authors: Komatsu, Masaaki, Waguri, Satoshi, Ueno, Takashi, Iwata, Junichi, Murata, Shigeo, Tanida, Isei, Ezaki, Junji, Mizushima, Noboru, Ohsumi, Yoshinori, Uchiyama, Yasuo, Kominami, Eiki, Tanaka, Keiji, Chiba, Tomoki
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 09.05.2005; The Rockefeller University Press
• Subjects: Animals; Animals, Newborn; Antibodies; Autophagy - genetics; Autophagy-Related Protein 7; Cell aggregates; Cell Line; Cellular biology; Fasting; Genes; Hepatocytes; Hepatocytes - metabolism; Hepatocytes - pathology; Hepatocytes - ultrastructure; Hepatomegaly - metabolism; Hepatomegaly - pathology; Hepatomegaly - physiopathology; Inclusion Bodies - metabolism; Inclusion Bodies - pathology; Inclusion Bodies - ultrastructure; Intracellular Membranes - metabolism; Intracellular Membranes - pathology; Intracellular Membranes - ultrastructure; Liver; Liver - abnormalities; Liver - metabolism; Liver - pathology; Membranes; Mice; Mice, Knockout; Microtubule-Associated Proteins - genetics; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; Mitochondria - ultrastructure; Nutrition; Organelles; Organelles - metabolism; Organelles - pathology; Organelles - ultrastructure; Phenotype; Proteins; Saccharomyces cerevisiae Proteins - genetics; Starvation; Starvation - metabolism; Ubiquitin - metabolism; Ubiquitins; Yeast
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200412022

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.