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Antagonistic control of muscle cell size by AMPK and mTORC1.

Abstract : Nutrition and physical activity have profound effects on skeletal muscle metabolism and growth. Regulation of muscle mass depends on a thin balance between growth-promoting and growth-suppressing factors. Over the past decade, the mammalian target of rapamycin (mTOR) kinase has emerged as an essential factor for muscle growth by mediating the anabolic response to nutrients, insulin, insulin-like growth factors and resistance exercise. As opposed to the mTOR signaling pathway, the AMP-activated protein kinase (AMPK) is switched on during starvation and endurance exercise to upregulate energy-conserving processes. Recent evidence indicates that mTORC1 (mTOR Complex 1) and AMPK represent two antagonistic forces governing muscle adaption to nutrition, starvation and growth stimulation. Animal knockout models with impaired mTORC1 signaling showed decreased muscle mass correlated with increased AMPK activation. Interestingly, AMPK inhibition in p70S6K-deficient muscle cells restores cell growth and sensitivity to nutrients. Conversely, muscle cells lacking AMPK have increased mTORC1 activation with increased cell size and protein synthesis rate. We also demonstrated that the hypertrophic action of MyrAkt is enhanced in AMPK-deficient muscle, indicating that AMPK acts as a negative feedback control to restrain muscle hypertrophy. Our recent results extend this notion by showing that AMPKα1, but not AMPKα2, regulates muscle cell size through the control of mTORC1 signaling. These results reveal the diverse functions of the two catalytic isoforms of AMPK, with AMPKα1 playing a predominant role in the control of muscle cell size and AMPKα2 mediating muscle metabolic adaptation. Thus, the crosstalk between AMPK and mTORC1 signaling is a highly regulated way to control changes in muscle growth and metabolic rate imposed by external cues.
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https://www.hal.inserm.fr/inserm-00625529
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Submitted on : Wednesday, August 15, 2012 - 7:00:08 AM
Last modification on : Thursday, April 9, 2020 - 11:54:38 AM
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Rémi Mounier, Louise Lantier, Jocelyne Leclerc, Athanassia Sotiropoulos, Marc Foretz, et al.. Antagonistic control of muscle cell size by AMPK and mTORC1.. Cell Cycle, Taylor & Francis, 2011, 10 (16), pp.2640-6. ⟨10.4161/cc.10.16.17102⟩. ⟨inserm-00625529⟩

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