Journal
CELL METABOLISM
Volume 10, Issue 6, Pages 507-515Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2009.10.008
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Funding
- Agenzia Spaziale Italiana
- Telethon [S04009]
- AFM [14135]
- Italian Ministry of Education, University and Research [PRIN 2007]
- Compagnia San Paolo
- European Union [223576]
- Japan Science and Technology Agency
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The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes for protein and organelle clearance. In skeletal muscle, both systems are under FoxO regulation and their excessive activation induces severe muscle loss. Although altered autophagy has been observed in various myopathies, the specific role of autophagy in skeletal muscle has not been determined by loss-of-function approaches. Here, we report that muscle-specific deletion of a crucial autophagy gene, Atg7, resulted in profound muscle atrophy and age-dependent decrease in force. Atg7 null muscles showed accumulation of abnormal mitochondria, sarcoplasmic reticulum distension, disorganization of sarcomere, and formation of aberrant concentric membranous structures. Autophagy inhibition exacerbated muscle loss during denervation and fasting. Thus, autophagy flux is important to preserve muscle mass and to maintain myofiber integrity. Our results suggest that inhibition/alteration of autophagy can contribute to myofiber degeneration and weakness in muscle disorders characterized by accumulation of abnormal mitochondria and inclusions.
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