FoxO3 controls autophagy in skeletal muscle in vivo - PubMed (original) (raw)
doi: 10.1016/j.cmet.2007.11.001.
Giulia Milan, Vanina Romanello, Eva Masiero, Ruediger Rudolf, Paola Del Piccolo, Steven J Burden, Raffaella Di Lisi, Claudia Sandri, Jinghui Zhao, Alfred L Goldberg, Stefano Schiaffino, Marco Sandri
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- PMID: 18054315
- DOI: 10.1016/j.cmet.2007.11.001
Free article
FoxO3 controls autophagy in skeletal muscle in vivo
Cristina Mammucari et al. Cell Metab. 2007 Dec.
Free article
Abstract
Autophagy allows cell survival during starvation through the bulk degradation of proteins and organelles by lysosomal enzymes. However, the mechanisms responsible for the induction and regulation of the autophagy program are poorly understood. Here we show that the FoxO3 transcription factor, which plays a critical role in muscle atrophy, is necessary and sufficient for the induction of autophagy in skeletal muscle in vivo. Akt/PKB activation blocks FoxO3 activation and autophagy, and this effect is not prevented by rapamycin. FoxO3 controls the transcription of autophagy-related genes, including LC3 and Bnip3, and Bnip3 appears to mediate the effect of FoxO3 on autophagy. This effect is not prevented by proteasome inhibitors. Thus, FoxO3 controls the two major systems of protein breakdown in skeletal muscle, the ubiquitin-proteasomal and autophagic/lysosomal pathways, independently. These findings point to FoxO3 and Bnip3 as potential therapeutic targets in muscle wasting disorders and other degenerative and neoplastic diseases in which autophagy is involved.
Comment in
- FoxO3 controls dangerous proteolytic liaisons.
Attaix D, Bechet D. Attaix D, et al. Cell Metab. 2007 Dec;6(6):425-7. doi: 10.1016/j.cmet.2007.11.005. Cell Metab. 2007. PMID: 18054311
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- R01 AR055027/AR/NIAMS NIH HHS/United States
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