title: Mitochondrial fission and remodelling contributes to muscle atrophy.
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.
authors.affiliation: Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Vanina
authors.initials: V
authors.lastname: Romanello
authors.forename: Eleonora
authors.initials: E
authors.lastname: Guadagnin
authors.forename: Ligia
authors.initials: L
authors.lastname: Gomes
authors.forename: Ira
authors.initials: I
authors.lastname: Roder
authors.forename: Claudia
authors.initials: C
authors.lastname: Sandri
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Petersen
authors.forename: Giulia
authors.initials: G
authors.lastname: Milan
authors.forename: Eva
authors.initials: E
authors.lastname: Masiero
authors.forename: Paola
authors.initials: P
authors.lastname: Del Piccolo
authors.forename: Marc
authors.initials: M
authors.lastname: Foretz
authors.forename: Luca
authors.initials: L
authors.lastname: Scorrano
authors.forename: Rudiger
authors.initials: R
authors.lastname: Rudolf
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002460:Cell Line; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D055372:AMP-Activated Protein Kinases
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