Details

Autor(en) / Beteiligte

• Spiegelman, Bruce M
• Lin, Jiandie
• Wu, Hai
• Tarr, Paul T
• Zhang, Chen-Yu
• Wu, Zhidan
• Boss, Olivier
• Michael, Laura F
• Puigserver, Pere
• Isotani, Eiji
• Olson, Eric N
• Lowell, Bradford B
• Bassel-Duby, Rhonda

Titel

Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres

Ist Teil von

• Nature (London), 2002-08, Vol.418 (6899), p.797-801

Ort / Verlag

London: Nature Publishing

Erscheinungsjahr

2002

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-γ co-activator-1 (PGC-1α), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1α is expressed preferentially in muscle enriched in type I fibres. When PGC-1α is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1α transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1α activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1α is a principal factor regulating muscle fibre type determination.