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MTORC1 determines autophagy through ULK1 regulation in skeletal muscle

Castets, Perrine and Rüegg, Markus A.. (2013) MTORC1 determines autophagy through ULK1 regulation in skeletal muscle. Autophagy, 9 (9). pp. 1435-1437.

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Official URL: http://edoc.unibas.ch/dok/A6183961

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Abstract

Autophagy impairment has been implicated in several muscle disorders and in age-related dysfunction. Although previous reports pointed to FOXO as a positive regulator of autophagy in skeletal muscle, it remained unclear what is triggering autophagy. We found that TSC muscle knockout (TSCmKO) mice, characterized by specific depletion of TSC1 in skeletal muscle, and thus constant activation of MTORC1, develop a late-onset myopathy marked by the accumulation of autophagic substrates. In those mice, autophagy induction is blocked despite FOXO activation because of constant MTORC1-dependent inhibition of ULK1. Treatment of TSCmKO mice with rapamycin is sufficient to restore autophagy and to alleviate, at least in part, the myopathy. Inversely, inactivation of the MTORC1 pathway in RPTOR-depleted muscles triggers LC3B lipidation in spite of FOXO inhibition. In conclusion, MTORC1 constitutes the master regulator of autophagy induction in skeletal muscle and its deregulation leads to pathologic alterations of muscle homeostasis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Taylor & Francis
ISSN:1554-8627
e-ISSN:1554-8635
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:27 Oct 2017 16:10
Deposited On:08 Nov 2013 08:29

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