Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction
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Finley-2012-Skeletal muscle tran.pdf
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Author(s)
Finley, Lydia W. S.
Lee, Jaewon
Souza, Amanda
Desquiret-Dumas, Valérie
Bullock, Kevin
Rowe, Glenn C.
Procaccio, Vincent
Clish, Clary
Arany, Zoltan
Haigis, Marcia C.
Date Issued
February 2012
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Finley, L. W. S. et al. “Skeletal Muscle Transcriptional Coactivator PGC-1 Mediates Mitochondrial, but Not Metabolic, Changes During Calorie Restriction.” Proceedings of the National Academy of Sciences 109.8 (2012): 2931–2936. Copyright ©2012 by the National Academy of Sciences
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Final published version
Abstract
Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation, and reactive oxygen species (ROS) scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1α is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1α activity. To test this model, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1α (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1α is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy (EM) demonstrated that PGC-1α is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1α is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1α nor mitochondrial biogenesis in skeletal muscle are required for the whole-body metabolic benefits of CR.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1073/pnas.1115813109
