2. Academic Validation
  3. Dexamethasone-induced autophagy mediates muscle atrophy through mitochondrial clearance

Dexamethasone-induced autophagy mediates muscle atrophy through mitochondrial clearance

  • Cell Cycle. 2014;13(14):2281-95. doi: 10.4161/cc.29272.
Rodrigo Troncoso 1,  Felipe Paredes 1,  Valentina Parra 2,  Damián Gatica 1,  César Vásquez-Trincado 1,  Clara Quiroga 1,  Roberto Bravo-Sagua 1,  Camila López-Crisosto 1,  Andrea E Rodriguez 1,  Alejandra P Oyarzún 1,  Guido Kroemer 3,  Sergio Lavandero 2
Affiliations

Affiliations

  • 1 Advanced Center for Chronic Disease (ACCDiS); University of Chile; Santiago, Chile; Center for Molecular Studies of the Cell; Faculty of Chemical & Pharmaceutical Sciences & Faculty of Medicine; University of Chile; Santiago, Chile.
  • 2 Advanced Center for Chronic Disease (ACCDiS); University of Chile; Santiago, Chile; Center for Molecular Studies of the Cell; Faculty of Chemical & Pharmaceutical Sciences & Faculty of Medicine; University of Chile; Santiago, Chile; Department of Internal Medicine (Cardiology Division); University of Texas Southwestern Medical Center; Dallas, TX USA.
  • 3 Equipe 11 labellisée pas la Ligue Nationale contre le Cancer; INSERM; Centre de Recherche des Cordeliers; Paris, France; Metabolomics and Cell Biology Platforms; Institut Gustave Roussy; Villejuif, France; Pôle de Biologie; Hôpital Européen Georges Pompidou; AP-HP; Paris, France; Université Paris Descartes; Paris Sorbonne Cité; Paris, France.
PMID: 24897381 DOI: 10.4161/cc.29272
Abstract

Glucocorticoids, such as dexamethasone, enhance protein breakdown via ubiquitin-proteasome system. However, the role of Autophagy in organelle and protein turnover in the glucocorticoid-dependent atrophy program remains unknown. Here, we show that dexamethasone stimulates an early activation of Autophagy in L6 myotubes depending on protein kinase, AMPK, and Glucocorticoid Receptor activity. Dexamethasone increases expression of several Autophagy genes, including ATG5, LC3, BECN1, and SQSTM1 and triggers AMPK-dependent mitochondrial fragmentation associated with increased DNM1L protein levels. This process is required for Mitophagy induced by dexamethasone. Inhibition of mitochondrial fragmentation by Mdivi-1 results in disrupted dexamethasone-induced Autophagy/Mitophagy. Furthermore, Mdivi-1 increases the expression of genes associated with the atrophy program, suggesting that Mitophagy may serve as part of the quality control process in dexamethasone-treated L6 myotubes. Collectively, these data suggest a novel role for dexamethasone-induced Autophagy/Mitophagy in the regulation of the muscle atrophy program.

Keywords

autophagy; dexamethasone; glucocorticoid; mitophagy; muscle atrophy.

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