PE in modulation of energy flux through OXPHOS

项目摘要 线粒体氧化磷酸化(OXPHOS)由发生在细胞内的一系列过程组成。 线粒体内膜(IMM)。通过OXPHOS的能量流动似乎内在地受到 IMM的脂质组成机制尚不清楚。尤其是磷脂酰基- 乙醇胺(PE)是一种锥形的非双层脂质，它能引起膜的弯曲并结合在一起 与线粒体呼吸复合体具有高亲和力，并调节其功能。我们发现 诱导高OXPHOS通量的干预措施伴随着线粒体PE的增加，因此 增加足以增加线粒体的呼吸能力。这项提议的中心前提是 为线粒体PE含量改变提供全面的生物能量学预测。结合了高- 分辨率呼吸计量学、荧光计量学、电生理学和显微镜，我们将研究PE在 以下过程：1)调节线粒体丙酮酸进入IMM以促进Warburg效应，2) 引起氧化应激的电子传递链中电子泄漏的来源和3)ATP的效率 通过合成来改变电池的燃油经济性。

Project Summary Mitochondrial oxidative phosphorylation (OXPHOS) consists of a series of processes that takes place in the inner mitochondrial membrane (IMM). Energy flux through OXPHOS appears to be intrinsically modulated by the lipid composition of IMM by mechanisms that are not clearly understood. In particular, phosphatidyl- ethanolamine (PE) is a cone-shaped non-bilayer lipid that induces membrane curvature in cristae and binds with high affinity to mitochondrial respiratory complexes and regulate their functions. We found that interventions that induce high OXPHOS flux are accompanied by increases in mitochondrial PE, and such increase was sufficient to increase mitochondrial respiratory capacity. The central premise of this proposal is to provide a comprehensive bioenergetics prognosis for altered mitochondrial PE content. Combining high- resolution respirometry, fluorometry, electrophysiology, and microscopy, we will examine the role of PE in the following processes: 1) Regulation of mitochondrial pyruvate entry at IMM to facilitate the Warburg effect, 2) Origin of electron leak in the electron transport chain to induce oxidative stress, and 3) Efficiency of ATP synthesis to alter cellular fuel economy.