Mitochondrial membrane lipids and respiratory efficiency

项目摘要 没有任何能量传递过程是完全有效的。线粒体氧化磷酸化（OXPHOS） 由一系列具有已知的低效能量传递节点的反应组成。运动训练是众所周知的 以提高骨骼肌线粒体的效率，最大限度地提高能量输出。这一提议的前提是 研究线粒体内膜（IMM）中的心磷脂（CL）如何调节OXPHOS效率， 改变骨骼肌和全身能量消耗。CL是一种锥形非双层脂质， 膜曲率在嵴，并结合高亲和力线粒体呼吸复合体，以调节 它们的功能。运动或不活动会改变肌肉线粒体CL含量，这与 OXPHOS效率。初步的组织特异性功能获得或丧失研究表明， 线粒体CL降低了OXPHOS保护小鼠免于饮食诱导的肥胖的效率。中央 该建议的假设是运动促进CL生物合成以提高OXPHOS能量效率。 结合线粒体诊断，脂质组学和代谢表型，CL在能量代谢中的作用 将检查转导。

Project Summary No energy transfer processes are perfectly efficient. Mitochondrial oxidative phosphorylation (OXPHOS) consists of a sequence of reactions with known nodes of inefficient energy transfer. Exercise training is known to improve skeletal muscle mitochondrial efficiency to maximize energy output. The premise of this proposal is to examine how cardiolipin (CL) in the inner mitochondrial membrane (IMM) modulates OXPHOS efficiency to alter skeletal muscle and whole-body energy expenditure. CL is a cone-shaped non-bilayer lipid that induces membrane curvature in cristae, and binds with high affinity to mitochondrial respiratory complexes to regulate their functions. Exercise or inactivity alters muscle mitochondrial CL content, coincidental to changes in OXPHOS efficiency. Preliminary tissue-specific gain- or loss-of-function studies suggest that reduced mitochondrial CL diminishes OXPHOS efficiency to protect mice from diet-induced obesity. The central hypothesis of this proposal is that exercise promotes CL biosynthesis to improve OXPHOS energy efficiency. Combining mitochondrial diagnostics, lipidomics, and metabolic phenotyping, the role of CL in energy transduction will be examined.