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

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

Research output: Contribution to journalArticle

Abstract

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 coactivator-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.

Original languageEnglish (US)
Pages (from-to)797-801
Number of pages5
JournalNature
Volume418
Issue number6899
DOIs
StatePublished - Aug 15 2002
Externally publishedYes

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Slow-Twitch Muscle Fibers
Muscles
Transgenic Mice
Skeletal Muscle
MM Form Creatine Kinase
Peroxisome Proliferator-Activated Receptors
Proteins
Troponin I
Brown Adipose Tissue
Mitochondrial Genes
Myoglobin
Calcineurin
Organelle Biogenesis
Muscle Cells
Fatigue
Cultured Cells
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Lin, J., Wu, H., Tarr, P. T., Zhang, C. Y., Wu, Z., Boss, O., ... Spiegelman, B. M. (2002). Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. Nature, 418(6899), 797-801. https://doi.org/10.1038/nature00904

Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. / Lin, Jiandie; Wu, Hai; Tarr, Paul T.; Zhang, Chen Yu; Wu, Zhidan; Boss, Olivier; Michael, Laura F.; Puigserver, Pere; Isotani, Elji; Olson, Eric N.; Lowell, Bradford B.; Bassel-Duby, Rhonda; Spiegelman, Bruce M.

In: Nature, Vol. 418, No. 6899, 15.08.2002, p. 797-801.

Research output: Contribution to journalArticle

Lin, J, Wu, H, Tarr, PT, Zhang, CY, Wu, Z, Boss, O, Michael, LF, Puigserver, P, Isotani, E, Olson, EN, Lowell, BB, Bassel-Duby, R & Spiegelman, BM 2002, 'Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres', Nature, vol. 418, no. 6899, pp. 797-801. https://doi.org/10.1038/nature00904
Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O et al. Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. Nature. 2002 Aug 15;418(6899):797-801. https://doi.org/10.1038/nature00904
Lin, Jiandie ; Wu, Hai ; Tarr, Paul T. ; Zhang, Chen Yu ; Wu, Zhidan ; Boss, Olivier ; Michael, Laura F. ; Puigserver, Pere ; Isotani, Elji ; Olson, Eric N. ; Lowell, Bradford B. ; Bassel-Duby, Rhonda ; Spiegelman, Bruce M. / Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. In: Nature. 2002 ; Vol. 418, No. 6899. pp. 797-801.
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