Mitochondrial fission and remodelling contributes to muscle atrophy |
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Authors: | Vanina Romanello Eleonora Guadagnin Ligia Gomes Ira Roder Claudia Sandri Yvonne Petersen Giulia Milan Eva Masiero Paola Del Piccolo Marc Foretz Luca Scorrano Rudiger Rudolf Marco Sandri |
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Institution: | 1. Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, Padova, Italy;2. Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany;3. Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Inserm, Paris, France;4. Department of Biomedical Science, University of Padova, Padova, Italy |
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Abstract: | Mitochondria are crucial organelles in the production of energy and in the control of signalling cascades. A machinery of pro‐fusion and fission proteins regulates their morphology and subcellular localization. In muscle this results in an orderly pattern of intermyofibrillar and subsarcolemmal mitochondria. Muscular atrophy is a genetically controlled process involving the activation of the autophagy‐lysosome and the ubiquitin–proteasome systems. Whether and how the mitochondria are involved in muscular atrophy is unknown. Here, we show that the mitochondria are removed through autophagy system and that changes in mitochondrial network occur in atrophying muscles. Expression of the fission machinery is per se sufficient to cause muscle wasting in adult animals, by triggering organelle dysfunction and AMPK activation. Conversely, inhibition of the mitochondrial fission inhibits muscle loss during fasting and after FoxO3 overexpression. Mitochondrial‐dependent muscle atrophy requires AMPK activation as inhibition of AMPK restores muscle size in myofibres with altered mitochondria. Thus, disruption of the mitochondrial network is an essential amplificatory loop of the muscular atrophy programme. |
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Keywords: | atrophy fission mitochondria skeletal muscle |
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