期刊
EMBO JOURNAL
卷 29, 期 10, 页码 1774-1785出版社
WILEY
DOI: 10.1038/emboj.2010.60
关键词
atrophy; fission; mitochondria; skeletal muscle
资金
- ASI
- Telethon Italy [TCP04009]
- Italian Ministry of Education, University and Research
- European Union [223576]
- DFG [RU923/3-1]
- AIRC Italy
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. The EMBO Journal (2010) 29, 1774-1785. doi: 10.1038/emboj.2010.60; Published online 16 April 2010
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据