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

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

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Mar 2019 14:03
Deposited On:22 Mar 2012 13:29

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