Transcriptional coactivator PGC-1 alpha 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

doi:10.1016/j.cmet.2005.03.002

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

Journal article

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Transcriptional coactivator PGC-1 alpha 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, …

Cell metabolism, Vol.1(4), pp.259-271

04/2005

DOI: 10.1016/j.cmet.2005.03.002

PMID: 16054070

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Abstract

Skeletal and cardiac muscle depend on high turnover of ATP made by mitochondria in order to contract efficiently. The transcriptional coactivator PGC-1alpha 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-1alpha 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-1alpha have a diminished ability to increase work output in response to chemical or electrical stimulation. As mice lacking PGC-1alpha age, cardiac dysfunction becomes evident in vivo. These data indicate that PGC-1alpha is vital for the heart to meet increased demands for ATP and work in response to physiological stimuli.

Animals

Trans-Activators - deficiency

Myocardium - metabolism

Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

Trans-Activators - genetics

Muscle, Skeletal - metabolism

Trans-Activators - metabolism

Mice

Mitochondria - metabolism

Transcription Factors

Muscle Fibers, Skeletal - metabolism

Mice, Knockout

Details

Title: Subtitle: Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle
Creators: Zoltan Arany - Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
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
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.1(4), pp.259-271
Publisher: United States
DOI: 10.1016/j.cmet.2005.03.002
PMID: 16054070
ISSN: 1550-4131
eISSN: 1932-7420
Grant note: HL06296 / NHLBI NIH HHS DK065584 / NIDDK NIH HHS DK61562 / NIDDK NIH HHS HL063985 / NHLBI NIH HHS HL07604 / NHLBI NIH HHS DK54477 / NIDDK NIH HHS HL052320 / NHLBI NIH HHS
Language: English
Date published: 04/2005
Academic Unit: Radiology; Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984025584402771

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