Mitochondrial membrane lipids and respiratory efficiency

线粒体膜脂和呼吸效率

• 批准号: 10444618
• 负责人: Katsuhiko Funai
• 金额: $ 47.29万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444618
• 关键词: ATP Synthesis Pathway; Ablation; Affect; Affinity; Anabolism; Binding; Cardiolipins; Complex; Cone; Consumption; Crista ampullaris; Data; Diagnostic; Electron Transport; Electrons; Electrophysiology (science); Energy Metabolism; Energy Transfer; Enzymes; Exercise; Exhibits; Fatty acid glycerol esters; Fluorometry; Genetic; Inner mitochondrial membrane; Lead; Membrane; Membrane Lipids; Metabolic; Microscopy; Mitochondria; Modeling; Mus; Muscle; Muscle Contraction; Muscle Mitochondria; Obesity; Obesity associated disease; Organ; Output; Oxidative Phosphorylation; Physical activity; Process; Proton-Motive Force; Protons; Public Health; Reaction; Resolution; Rest; Role; Skeletal Muscle; Testing; Tissues; United States; Vesicle; comorbidity; cost; diet-induced obesity; electron donor; electron energy; exercise training; improved; lipidomics; loss of function; metabolic phenotype; metabolic rate; mitochondrial membrane; mouse model; novel therapeutic intervention; obesity treatment; oligomycin sensitivity-conferring protein; overweight adults; respiratory; voltage

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.

项目概要 没有任何能量转移过程是完全有效的。线粒体氧化磷酸化 (OXPHOS) 由一系列具有已知低效能量转移节点的反​​应组成。运动训练众所周知 提高骨骼肌线粒体效率，最大限度地提高能量输出。这个提议的前提是 检查线粒体内膜 (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，可诱导 嵴中的膜曲率，并以高亲和力与线粒体呼吸复合物结合以调节 他们的职能。运动或不活动会改变肌肉线粒体 CL 含量，与 OXPHOS 效率。初步的组织特异性功能获得或丧失研究表明，减少 线粒体 CL 降低 OXPHOS 效率，保护小鼠免受饮食引起的肥胖。中央 该提案的假设是运动促进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分析，CL 在能量中的作用 将检查转导。