PE in modulation of energy flux through OXPHOS

PE 通过 OXPHOS 调节能量通量

• 批准号: 10665081
• 负责人: Katsuhiko Funai
• 金额: $ 30.5万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665081
• 关键词: ATP Synthesis Pathway; Adenocarcinoma; Affect; Affinity; Architecture; Binding; Bioenergetics; Carnitine; Chemicals; Complex; Cone; Consumption; Crista ampullaris; Disease; Electron Transport; Electrons; Electrophysiology (science); Exercise; Fluorometry; Health; Impairment; Inner mitochondrial membrane; Intervention; Intestines; Lipids; Liver Mitochondria; Membrane; Membrane Potentials; Microscopy; Mitochondria; Modeling; Mus; Muscle Mitochondria; Outer Mitochondrial Membrane; Oxidation-Reduction; Oxidative Phosphorylation; Oxidative Stress; Oxidative Stress Induction; Phosphatidylethanolamine; Play; Process; Prognosis; Proton-Motive Force; Protons; Pyruvate; Reaction; Regulation; Research; Resolution; Respiration; Role; Series; Shapes; Skeletal Muscle; Spirometry; Steatohepatitis; Surface; Testing; Transferase; Warburg Effect; body system; cell type; diagnostic platform; electron donor; electron energy; energy efficiency; exercise training; fatty liver disease; improved; mitochondrial membrane; oligomycin sensitivity-conferring protein; pyruvate carrier; respiratory; stem cells; tumorigenesis

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.

项目概要 线粒体氧化磷酸化（OXPHOS）由发生在线粒体中的一系列过程组成。 线粒体内膜（IMM）。通过 OXPHOS 的能量通量似乎本质上受到以下因素的调节 IMM 的脂质组成的机制尚不清楚。特别是，磷脂酰 乙醇胺 (PE) 是一种锥形非双层脂质，可诱导嵴膜弯曲并结合 与线粒体呼吸复合物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，等等 增加足以增加线粒体呼吸能力。该提案的中心前提是 为改变的线粒体 PE 含量提供全面的生物能学预测。结合高 分辨率呼吸测定法、荧光测定法、电生理学和显微镜检查，我们将研究 PE 在 以下过程：1) 调节 IMM 中的线粒体丙酮酸进入以促进 Warburg 效应，2) 电子传递链中电子泄漏引发氧化应激的根源，以及 3) ATP 效率 合成以改变细胞燃料经济性。