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

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 - J. Cell Biol. (2005)

Bottom Line: Autophagy is a membrane-trafficking mechanism that delivers cytoplasmic constituents into the lysosome/vacuole for bulk protein degradation.Aberrant autophagy has been reported in several neurodegenerative disorders, hepatitis, and myopathies.Furthermore, Atg7 deficiency led to multiple cellular abnormalities, such as appearance of concentric membranous structure and deformed mitochondria, and accumulation of ubiquitin-positive aggregates.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.

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.

Show MeSH

Related in: MedlinePlus

Electron micrographs of hepatic cells with Atg7 deficiency. (A and B) Note the presence of concentric membranous structures in the mutant cells (arrowheads). Higher magnification view (B) shows the membranous elements are continuous with the rough ER (arrowheads). (C and D) The mutant cells contained a high number of peroxisomes (arrows) and deformed mitochondria (asterisks). Insets show higher magnification views. Nuc, nucleus. Bars: (A) 5 μm; (B) 0.5 μm; (C and D) 1 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2171928&req=5

fig6: Electron micrographs of hepatic cells with Atg7 deficiency. (A and B) Note the presence of concentric membranous structures in the mutant cells (arrowheads). Higher magnification view (B) shows the membranous elements are continuous with the rough ER (arrowheads). (C and D) The mutant cells contained a high number of peroxisomes (arrows) and deformed mitochondria (asterisks). Insets show higher magnification views. Nuc, nucleus. Bars: (A) 5 μm; (B) 0.5 μm; (C and D) 1 μm.

Mentions: Although most hepatocytes were still alive in the mutant liver, ultrastructural analysis revealed the appearance of aberrant concentric membranous structures (Fig. 6, A and B), which were also observed as early as 20 d after pIpC-injected liver (not depicted). These structures surrounded various cytoplasmic constituents such as mitochondria, lipid droplets, and vesicular structures (Fig. 6 A). Their membranous elements were continuous with the rough ER (Fig. 6 B, arrowheads), and the corresponding structures were positive for calreticulin, an ER protein marker (not depicted), indicating that these structures originated from the rough ER. Accumulation of peroxisomes (Fig. 6 C) and deformed mitochondria (Fig. 6, C and D) was also observed in the mutant liver. These results suggest the important role of autophagy in turnover of organelles, and its defect results in accumulation of abnormal organelles.


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

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 - J. Cell Biol. (2005)

Electron micrographs of hepatic cells with Atg7 deficiency. (A and B) Note the presence of concentric membranous structures in the mutant cells (arrowheads). Higher magnification view (B) shows the membranous elements are continuous with the rough ER (arrowheads). (C and D) The mutant cells contained a high number of peroxisomes (arrows) and deformed mitochondria (asterisks). Insets show higher magnification views. Nuc, nucleus. Bars: (A) 5 μm; (B) 0.5 μm; (C and D) 1 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171928&req=5

fig6: Electron micrographs of hepatic cells with Atg7 deficiency. (A and B) Note the presence of concentric membranous structures in the mutant cells (arrowheads). Higher magnification view (B) shows the membranous elements are continuous with the rough ER (arrowheads). (C and D) The mutant cells contained a high number of peroxisomes (arrows) and deformed mitochondria (asterisks). Insets show higher magnification views. Nuc, nucleus. Bars: (A) 5 μm; (B) 0.5 μm; (C and D) 1 μm.
Mentions: Although most hepatocytes were still alive in the mutant liver, ultrastructural analysis revealed the appearance of aberrant concentric membranous structures (Fig. 6, A and B), which were also observed as early as 20 d after pIpC-injected liver (not depicted). These structures surrounded various cytoplasmic constituents such as mitochondria, lipid droplets, and vesicular structures (Fig. 6 A). Their membranous elements were continuous with the rough ER (Fig. 6 B, arrowheads), and the corresponding structures were positive for calreticulin, an ER protein marker (not depicted), indicating that these structures originated from the rough ER. Accumulation of peroxisomes (Fig. 6 C) and deformed mitochondria (Fig. 6, C and D) was also observed in the mutant liver. These results suggest the important role of autophagy in turnover of organelles, and its defect results in accumulation of abnormal organelles.

Bottom Line: Autophagy is a membrane-trafficking mechanism that delivers cytoplasmic constituents into the lysosome/vacuole for bulk protein degradation.Aberrant autophagy has been reported in several neurodegenerative disorders, hepatitis, and myopathies.Furthermore, Atg7 deficiency led to multiple cellular abnormalities, such as appearance of concentric membranous structure and deformed mitochondria, and accumulation of ubiquitin-positive aggregates.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.

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.

Show MeSH
Related in: MedlinePlus