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, Eiji Isotani, Eric N. Olson, Bradford B. Lowell, Rhonda Bassel-Duby and Bruce M. Spiegelman ()
Additional contact information
Jiandie Lin: Harvard Medical School
Hai Wu: University of Texas Southwestern Medical Center
Paul T. Tarr: Harvard Medical School
Chen-Yu Zhang: Harvard Medical School
Zhidan Wu: Harvard Medical School
Olivier Boss: Harvard Medical School
Laura F. Michael: Harvard Medical School
Pere Puigserver: Harvard Medical School
Eiji Isotani: University of Texas Southwestern Medical Center
Eric N. Olson: University of Texas Southwestern Medical Center
Bradford B. Lowell: Harvard Medical School
Rhonda Bassel-Duby: University of Texas Southwestern Medical Center
Bruce M. Spiegelman: Harvard Medical School

Nature, 2002, vol. 418, issue 6899, 797-801

Abstract: 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) fibres1. 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 metabolism2,3,4. 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.

Date: 2002
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature00904 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:418:y:2002:i:6899:d:10.1038_nature00904

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature00904

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().