Autophagy Is Required to Maintain Muscle Mass

641Citations
Citations of this article
530Readers
Mendeley users who have this article in their library.

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. © 2009 Elsevier Inc. All rights reserved.

Author supplied keywords

Cite

CITATION STYLE

APA

Masiero, E., Agatea, L., Mammucari, C., Blaauw, B., Loro, E., Komatsu, M., … Sandri, M. (2009). Autophagy Is Required to Maintain Muscle Mass. Cell Metabolism, 10(6), 507–515. https://doi.org/10.1016/j.cmet.2009.10.008

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free