Regulation of autophagy and the ubiquitin–proteasome system by the FoxO transcriptional network during muscle atrophy
By G. Milan, V. Romanello, F. Pescatore, A. Armani, J. Paik, Laura Frasson, A. Seydel, Jinghui Zhao, Reimar Abraham, A. Goldberg and 3 more. Nature Communications, 2015
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Stresses like low nutrients, systemic inflammation, cancer or infections provoke a catabolic state characterized by enhanced muscle proteolysis and amino acid release to sustain liver gluconeogenesis and tissue protein synthesis. These conditions activate the family of Forkhead Box (Fox) O transcription factors. Here we report that muscle-specific deletion of FoxO members protects from muscle loss as a result of the role of FoxOs in the induction of autophagy–lysosome and ubiquitin–proteasome systems. Notably, in the setting of low nutrient signalling, we demonstrate that FoxOs are required for Akt activity but not for mTOR signalling. FoxOs control several stress–response pathways such as the unfolded protein response, ROS detoxification, DNA repair and translation. Finally, we identify FoxO-dependent ubiquitin ligases including MUSA1 and a previously uncharacterised ligase termed SMART (Specific of Muscle Atrophy and Regulated by Transcription). Our findings underscore the central function of FoxOs in coordinating a variety of stress-response genes during catabolic conditions. FoxO transcription factors promote muscle atrophy in response to stresses such as low nutrient availability. By generating muscle-specific FoxO triple-knockout mice, Milan et al.identify mechanisms by which the FoxO transcriptional network coordinates autophagic and proteasomal protein degradation.
Subfields: Aging, Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/2258aed16b2e41024cc5348d9f240f90bb2f0680
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Citations in the corpus
- Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children (2020, background): “However, potential adverse side effects of corticosteroid therapy include hyperglycemia (314, 315), catabolism-related diffuse neuromuscular weakness (including the diaphragm) (316, 317), and hospital-acquired infections (318).”
- Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy (2020, background): “found that a group of ubiquitin ligases were upregulated in denervated or fasted skeletal muscle, and were blunted in FoxO1, -3, and -4 triple knockout mice (FoxO1,3,4-/-) [47].”