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Abstract
Exercise triggers a pleiotropic response in skeletal muscle, which results in a profound remodeling of this tissue. Physical activity–dependent muscle fiber plasticity is regulated by a number of distinct signaling pathways. Even though most of these pathways are activated by different stimuli and in a temporally and spatially separated manner during exercise, many of the major signal transduction events converge on the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) by post-translationally modifying the PGC-1α protein, modulating PGC-1α gene expression or both. In turn, depending on the cellular context, PGC-1α regulates specific gene programs. Ultimately, PGC-1α modulates most of the transcriptional adaptations of skeletal muscle to exercise. In this review, the regulation and function of this pivotal transcriptional coactivator in muscle are discussed.
Acknowledgements
I thank my colleagues for discussions, ideas, and suggestions for writing this manuscript and Christian Gasser, Institute of Physiology, University of Zurich for help with the artwork. I apologize for the omission of several important contributions due to space constraints.
Declaration of interest
The author declares no conflict of interest. Our research is supported by grants from the Swiss National Science Foundation (SNF PP00A-110746), the Muscular Dystrophy Association USA (MDA68442), the SwissLife “Jubiläumsstiftung für Volksgesundheit und medizinische Forschung”, the Swiss Society for Research on Muscle Diseases (SSEM), the United Mitochondrial Disease Foundation (UMDF), the Association Française contre les myopathies (AFM), the Roche Research Foundation, SystemsX.ch (the Swiss initiative in systems biology), and the University of Basel. The funders had no role in the preparation of the manuscript.