Mitochondrial biogenesis in skeletal muscle

这项研究建议旨在继续我们正在进行的工作，调查肌肉由于定期进行锻炼而发生的适应。我们使用细胞生物学、生化和分子方法来理解这一过程。肌肉对运动的一个重要适应是它在细胞内产生能量(ATP)的能力提高，称为线粒体。线粒体被称为细胞的“发动机”，因为它产生肌肉收缩所需的能量，对维持肌肉良好的新陈代谢健康很重要。经常进行的体力活动(即锻炼)会增加肌肉细胞的线粒体含量，这是一种适应，可以减少疲劳，改善各级体力活动的新陈代谢。已知这种适应发生在包括人类在内的各种动物物种中。这是如何发生的，目前还不完全清楚。这项建议的目的是调查我们认为在运动诱导的肌肉线粒体合成和周转过程中目前尚未解决的最重要、最前沿的研究问题。我们使用动物模型或培养的肌肉细胞，从基因转录、蛋白质易位以及肌肉线粒体对急性或慢性运动的反应水平上进行了研究。我们的研究项目的结果将对我们如何看待线粒体在肌肉细胞中的重要性产生重大影响，并将使我们能够修改我们对运动对细胞的好处以及线粒体周转在肌肉健康中的作用的想法。

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 called the “powerhouse” of the cell, because it generates the energy required for muscle to contract, and it is important for the maintenance of good muscle metabolic health. 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. This adaptation is 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 feel are the most important, cutting-edge research questions that are currently unresolved in the process of exercise-induced mitochondrial synthesis and turnover in muscle. We investigate this at the level of gene transcription, protein translocation and the movement and assembly of mitochondria in muscle responding to either acute or chronic exercise, using animal models or muscle cells in culture. The results of our research program will have a significant impact on how we view the importance of mitochondria within the context of the muscle cell, and will allow us to revise our thinking about the cellular benefits of exercise and the role of mitochondrial turnover in muscle health.