Premium
Mitochondrial fission and remodelling contributes to muscle atrophy
Author(s) -
Romanello Vanina,
Guadagnin Eleonora,
Gomes Ligia,
Roder Ira,
Sandri Claudia,
Petersen Yvonne,
Milan Giulia,
Masiero Eva,
Del Piccolo Paola,
Foretz Marc,
Scorrano Luca,
Rudolf Rudiger,
Sandri Marco
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.60
Subject(s) - mitochondrial fission , biology , mitochondrion , autophagy , microbiology and biotechnology , ampk , mitochondrial fusion , mfn2 , atrophy , muscle atrophy , mitophagy , mitochondrial dna , biochemistry , apoptosis , genetics , protein kinase a , phosphorylation , gene
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.