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J Physiol Pharmacol. 2008 Dec;59 Suppl 7:5-18.

Regulation by exercise of skeletal muscle content of mitochondria and GLUT4.

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Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.


Endurance exercise-training results in an increase in the size and number of mitochondria in the skeletal muscles that are involved in the exercise. In early studies of this phenomenon, long-term training programs of progressively increasing intensity and duration were used. These studies gave the impression that the adaptive increase in mitochondria is a slow process. Recent advances in the understanding of how mitochondrial biogenesis is regulated, have made it possible to study the mechanisms by which exercise regulates mitochondrial biogenesis. These studies have shown that a single bout of exercise induces a rapid increase in mitochondrial biogenesis that is mediated both by activation and by increased expression of a transcription coactivator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha). PGC-1alpha docks on and coactivates transcription factors that regulate expression of nuclear genes that encode mitochondrial proteins and also of the nuclear gene that encodes mitochondrial transcription factor A (TFAM). TFAM regulates mitochondrial DNA transcription. Thus, PGC-1alpha regulates the coordinated expression of mitochondrial proteins encoded in both nuclear and mitochondrial genes. In addition to an increase in mitochondrial biogenesis, exercise induces an increase in the GLUT4 isoform of the glucose transporter. This increase in GLUT4 occurs in parallel with, and is mediated by, the same signals and some of the same transcription factors as the increase in mitochondrial biogenesis. Two signals generated during exercise, the increase in cytosolic Ca(2+) and the decrease in high energy phosphates, mediate the activation and increased expression of PGC-1alpha. The purpose of this article is to present an overview of what is known regarding these phenomena.

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