Mechanisms controlling mitochondrial content and function in skeletal muscle

点击翻译按钮获取中文摘要

The ability of skeletal muscle to generate force is determined, in part, by the ability of mitochondria within muscle to utilize carbohydrates and fats and generate energy. The function of mitochondria within skeletal muscle is therefore an important determinant of exercise capacity, exercise tolerance, and quality of life. Changes in mitochondrial content occur because of changes in the transcriptional activity of an enzyme called Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). The activity of PGC-1alpha is proposed to be regulated by another enzyme called Sirtuin 1 (SIRT1) however the role of SIRT1 in increased mitochondrial content via activation PGC-1alpha in skeletal muscle is not fully understood. Another Sirtuin, SIRT3, is also believed to play a role mitochondrial function by helping activate energy production in mitochondria through the activation of PDH. SIRT3 may also play a role in the upregulation of mitochondrial content following exercise training via the activation of LRP130. Neither of these effects of SIRT3 have been examined in skeletal muscle. The proposed research program will examine the role of SIRT1 in exercise induced activation of PGC-1alpha and the importance of SIRT3 in determining mitochondrial function. We will use cutting edge molecular techniques to examine changes in SIRT1 and SIRT3 activity following a single bout of exercise and following exercise training via the activation of LRP130. We will also examine the mechanism(s) by which SIRT1 and SIRT3 alter muscle function by measuring changes in the molecular structure of their targets. The proposed research will impact our understanding of how muscle works, and our understanding of the mechanisms that underlying normal muscle function. We will expand our current knowledge surrounding the roles of SIRT1 and SIRT3 in human skeletal muscle, will potentially provide evidence regarding human physiology that has the potential to directly impact the Canadian population. More specifically, by furthering our understanding of how mitochondrial content and function are controlled in human skeletal muscle our basic research will provide information that can be used by applied scientists to help improve physical fitness and performance as well as health in Canadians. This research program will also provide opportunities for undergraduate and graduate students to learn the research process, while contributing to high quality research.