Mitochondrial energetics and fusion: role of the forkhead protein FOXC2

这项研究旨在实质性地推进对身体细胞内能量转换过程的理解。细胞中的能量转换过程远非完美——尽管人们对其机制了解甚少。例如，众所周知，将葡萄糖形式的能量转化为“细胞的通用能量货币”，即三磷酸腺苷，由于线粒体质子泄漏的过程而效率低下。质子泄漏的机制尚不清楚，但质子泄漏可能占肌肉静息能量代谢的50%。线粒体确实是细胞的“发电站”，负责广泛的代谢过程，包括ATP合成。在过去的十年里，已经有令人信服的证据表明，线粒体并不是许多教科书中描述的静态的椭圆形结构。事实上，它们不断地经历聚变和裂变循环。最近的证据表明，线粒体结构影响效率。自由基/活性氧的产生也会受到影响。拟议的研究将专门研究线粒体融合对效率和氧化应激的影响。因此，影响延伸到肥胖和衰老。

This research aims to substantially advance the understanding of energy conversion processes within cells of the body. Energy conversion processes in cells is far from perfect - though the mechanisms are very poorly understood. For example, it is known that the conversion of energy in the form of glucose to the 'universal energy currency of cells', adenosine triphosphate, is inefficient due to a process called mitochondrial proton leak. The mechanisms underlying proton leak are not well understood, but proton leak may account for up to 50% of the resting energy metabolism in muscle. Mitochondria are indeed the 'power-houses' of cells, responsible for a wide range of metabolic processes, including ATP synthesis. Over the last decade, it has been convincingly demonstrated that mitochondria are not the static oblong-shaped structures depicted in many textbooks. In fact, they are constantly undergoing fusion and fission cycles. Recent evidence suggests that mitochondrial structure impacts efficiency. Also affected is the production of free radicals/ reactive oxygen species. The proposed research will specifically examine the effects of mitochondrial fusion on efficiency and oxidative stress. Implications thus extend to obesity and aging.