Transcriptional coactivator PGC-1α controls the energy state and contractile function of cardiac muscle

Zoltan Arany, Huamei He, Jiandie Lin, Kirsten Hoyer, Christoph Handschin, Okan Toka, Ferhaan Ahmad, Takashi Matsui, Sherry Chin, Pei Hsuan Wu, Igor I. Rybkin, John M. Shelton, Monia Manieri, Saverio Cinti, Frederick J. Schoen, Rhonda Bassel-Duby, Anthony Rosenzweig, Joanne S. Ingwall, Bruce M. Spiegelman

Research output: Contribution to journalArticle

457 Scopus citations

Abstract

Skeletal and cardiac muscle depend on high turnover of ATP made by mitochondria in order to contract efficiently. The transcriptional coactivator PGC-1α has been shown to function as a major regulator of mitochondrial biogenesis and respiration in both skeletal and cardiac muscle, but this has been based only on gain-of-function studies. Using genetic knockout mice, we show here that, while PGC-1α KO mice appear to retain normal mitochondrial volume in both muscle beds, expression of genes of oxidative phosphorylation is markedly blunted. Hearts from these mice have reduced mitochondrial enzymatic activities and decreased levels of ATP. Importantly, isolated hearts lacking PGC-1α have a diminished ability to increase work output in response to chemical or electrical stimulation. As mice lacking PGC-1α age, cardiac dysfunction becomes evident in vivo. These data indicate that PGC-1α is vital for the heart to meet increased demands for ATP and work in response to physiological stimuli.

Original languageEnglish (US)
Pages (from-to)259-271
Number of pages13
JournalCell Metabolism
Volume1
Issue number4
DOIs
StatePublished - Apr 1 2005

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Arany, Z., He, H., Lin, J., Hoyer, K., Handschin, C., Toka, O., Ahmad, F., Matsui, T., Chin, S., Wu, P. H., Rybkin, I. I., Shelton, J. M., Manieri, M., Cinti, S., Schoen, F. J., Bassel-Duby, R., Rosenzweig, A., Ingwall, J. S., & Spiegelman, B. M. (2005). Transcriptional coactivator PGC-1α controls the energy state and contractile function of cardiac muscle. Cell Metabolism, 1(4), 259-271. https://doi.org/10.1016/j.cmet.2005.03.002