Mitochondrial biogenesis in skeletal muscle

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This research proposal is designed to continue our ongoing work in investigating the adaptations that take place in muscle as a result of regularly performed exercise. We use cell biology, biochemical and molecular approaches to understanding this process. A major adaptation that is well established in muscle in response to exercise is its improved ability to produce energy (ATP) within the cellular compartment called the mitochondrion. The mitochondrion is the "Powerhouse" of the cell, because it generates energy required for muscle to contract, and for endurance to be sustained. Regularly performed physical activity (i.e. exercise) produces an increase in the mitochondrial content of muscle cells, an adaptation that results in reduced fatigue and improved metabolism at all levels of physical activity. In contrast, in response to reduced activity, mitochondrial content declines. These adaptations are known to occur across a wide range of animal species, including humans. How this takes place is not fully understood. This purpose of this proposal is to investigate what we believe are important new aspects of mitochondrial synthesis and turnover at the level of gene transcription, mRNA stability, and the control of mitochondrial movements within muscle cells. All of these issues are critical in advancing our research program devoted to understanding how mitochondria function in muscle, and the effects of exercise.