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Article Addendum

Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle

Cristina Mammucari, Stefano Schiaffino and Marco Sandri

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The balance between synthesis and degradation of intracellular components determines the overall muscle fiber size. Muscle atrophy occurs when the degradation rate is higher than the synthesis rate, for example during disuse, fasting or systemic diseases such as diabetes, cancer and renal failure. The two main catabolic systems that are activated during atrophy are the ubiquitin-proteasome and the autophagy-lysosome pathways. FoxO3 transcription factor causes marked atrophy in adult skeletal muscle and induces the musclespecific ubiquitin ligase Atrogin-1/MAFbx.1 In addition, we recently reported that FoxO3 is necessary and sufficient for the induction of autophagy in skeletal muscle.2 Transcription of autophagy related genes, such as LC3B and Bnip3, is activated during fasting and is mediated by FoxO3. In particular, Bnip3 induces autophagosome formation and is responsible for the induction of autophagy by FoxO3. Surprisingly, rapamycin is not able to induce autophagy in skeletal muscle in vivo, indicating that the Akt-FoxO axis, rather than the Akt-mTOR pathway, is involved in this process. Here we discuss the major implications of our recent work.

Addendum to: Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C, Zhao J, Goldberg AL, Schiaffino S, Sandri M. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 2007; 6:458-71.

Authors

Cristina Mammucari

University of Padova

Stefano Schiaffino

University of Padova

Marco Sandri

University of Padova

Purchase article for $19

Subscribe to this journal for $99/year