PE in modulation of energy flux through OXPHOS

项目摘要 线粒体氧化磷酸化（OXPHOS）由一系列发生在线粒体中的过程组成。 线粒体内膜（IMM）。通过OXPHOS的能量通量似乎是由 IMM的脂质组成的机制尚不清楚。特别地，磷脂酰- 乙醇胺（PE）是一种锥形非双层脂质，可诱导嵴中的膜弯曲并结合 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通量的干预伴随着线粒体PE的增加， 增加足以增加线粒体呼吸能力。这一建议的核心前提是， 为改变的线粒体PE含量提供全面的生物能量学预测。结合高- 分辨率呼吸测定法，荧光测定法，电生理学和显微镜，我们将研究PE在 以下过程：1）在IMM处调节线粒体丙酮酸进入以促进瓦尔堡效应，2） 诱导氧化应激的电子传递链中电子泄漏的起源，以及3）ATP的效率 合成以改变蜂窝燃料经济性。

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.