Article

Autophagy is required to maintain muscle mass.

Dulbecco Telethon Institute, 35129 Padova, Italy.
Cell metabolism (impact factor: 17.35). 12/2009; 10(6):507-15. DOI:10.1016/j.cmet.2009.10.008 pp.507-15
Source: PubMed

ABSTRACT 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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Keywords

aberrant concentric membranous structures
 
abnormal mitochondria
 
age-dependent decrease
 
Atg7 null muscles
 
autophagy flux
 
Autophagy inhibition exacerbated muscle loss
 
autophagy-lysosome pathways
 
crucial autophagy gene
 
denervation
 
excessive activation induces severe muscle loss
 
FoxO regulation
 
inhibition/alteration
 
muscle disorders
 
muscle mass
 
muscle-specific deletion
 
myofiber degeneration
 
profound muscle atrophy
 
sarcoplasmic reticulum distension
 
skeletal muscle
 
two major routes