Dexamethasone-induced autophagy mediates muscle atrophy through mitochondrial clearance
| Autor: | Guido Kroemer, Rodrigo Troncoso, Sergio Lavandero, Andrea E. Rodriguez, Alejandra P. Oyarzún, Clara Quiroga, César Vásquez-Trincado, Damián Gatica, Valentina Parra, Roberto Bravo-Sagua, Felipe Paredes, Camila López-Crisosto |
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| Rok vydání: | 2014 |
| Předmět: |
Dynamins
Sequestosome-1 Protein medicine.medical_specialty Time Factors Muscle Fibers Skeletal ATG5 AMP-Activated Protein Kinases Biology Transfection Dexamethasone Autophagy-Related Protein 5 Cell Line DNM1L Receptors Glucocorticoid AMP-activated protein kinase Report Internal medicine Mitophagy Autophagy medicine Animals Glucocorticoids Molecular Biology Heat-Shock Proteins Quinazolinones Dose-Response Relationship Drug Proteins Cell Biology BECN1 Muscle atrophy Mitochondria Muscle Rats Cell biology Muscular Atrophy Endocrinology biology.protein Beclin-1 RNA Interference medicine.symptom Apoptosis Regulatory Proteins Microtubule-Associated Proteins Signal Transduction Developmental Biology |
| Zdroj: | CELL CYCLE (GEORGETOWN, TEX.) Artículos CONICYT CONICYT Chile instacron:CONICYT |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.29272 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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