PE in modulation of energy flux through OXPHOS

PE 通过 OXPHOS 调节能量通量

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要线粒体氧化磷酸化（OXPHOS）由发生在该过程中的一系列过程内部线粒体膜（IMM）。通过Oxphos的能量通量似乎是由 IMM的脂质组成是通过未清楚理解的机制的。特别是，磷脂酰基 - 乙醇胺（PE）是一种锥形的非双层脂质，可诱导Cristae膜曲率并结合对线粒体呼吸复合物的亲和力很高，并调节其功能。我们发现诱导高氧气通量的干预措施伴随着线粒体PE的增加，此类增加足以增加线粒体呼吸能力。该提议的主要前提是为线粒体PE含量改变提供了全面的生物能预后。结合高 - 分辨率呼吸测定法，荧光测定法，电生理学和显微镜，我们将检查PE在PE中的作用以下过程：1）对IMM处的线粒体丙酮酸进入以促进Warburg效应的调节，2）电子传输链中电子泄漏的起源以诱导氧化应激，3）ATP的效率综合改变细胞燃料经济性。