Regulation of mitochondrial respiratory complex I

线粒体呼吸复合物 I 的调节

• 批准号: 8031712
• 负责人: Yidong Bai
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-16 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8031712
• 关键词: Applications Grants; Cell Line; Cell model; Cells; Complex; Cytochrome c Reductase; Disease; Enzymes; Functional disorder; Gene Mutation; Genes; Genetic; Genome; Glutathione S-Transferase; Human; Human Genetics; Light; Medical; Metabolic Diseases; Methods; Mitochondria; Mitochondrial DNA; Mitochondrial Diseases; Mutation; NADH dehydrogenase (ubiquinone); Nuclear; Oxidative Phosphorylation; Pathogenesis; Pathway interactions; Patients; Play; Proteins; Regulation; Respiration; Respiratory Chain; Role; Structure; System; Testing; Therapeutic; Transferase; Up-Regulation; Work; human disease; interest; mitochondrial DNA mutation; novel strategies; protein complex; public health relevance; respiratory; restoration; success; vector

DESCRIPTION (provided by applicant): The mammalian NADH dehydrogenase (complex I), which is under dual genetic control, nuclear and mitochondrial, plays a central role in oxidative phosphorylation. This respiratory complex consists of 45 subunits and has been implicated in human genetic and acquired diseases. In previous studies, we have isolated several cell lines deficient in complex I assembly and mitochondrial function. We further identified a putative protein factor whose over-expression was associated with recovered complex I assembly. The specific aims of the proposal are to 1) determine if the protein we identified is a complex I assembly factor 2) to develop a genetic approach to isolated genes that could compensate mitochondrial deficiency caused by complex I gene mutations. The success of this proposal will help us to understand the regulation of assembly and function of respiratory complex I, and also provide useful clues for developing a therapeutic approach for complex I deficiency. PUBLIC HEALTH RELEVANCE: We submit this grant application focusing on understanding the function and regulation of mitochondrial respiratory complex I. In particular, we will develop a novel approach to isolate important protein factors which regulate mitochondrial function. The success of this project will advance our understanding of mitochondrial function and shed light on the pathogenesis of human disease associated with complex I dysfunction.

描述（由申请人提供）：哺乳动物NADH脱氢酶（复合物I）受细胞核和线粒体双重遗传控制，在氧化磷酸化中起核心作用。这种呼吸复合物由45个亚基组成，与人类遗传和获得性疾病有关。在以前的研究中，我们已经分离出几个细胞系缺乏复合物I组装和线粒体功能。我们进一步确定了一个假定的蛋白质因子，其过度表达与恢复复合物I组装。该提案的具体目标是：1）确定我们鉴定的蛋白质是否是复合物I组装因子2）开发一种分离基因的遗传方法，可以补偿由复合物I基因突变引起的线粒体缺陷。该方案的成功将有助于我们了解呼吸复合物I的组装和功能调节，也为开发复合物I缺乏症的治疗方法提供有用的线索。 公共卫生关系：我们提交了这项资助申请，重点是了解线粒体呼吸复合物I的功能和调节。特别是，我们将开发一种新的方法来分离调节线粒体功能的重要蛋白质因子。该项目的成功将推进我们对线粒体功能的理解，并阐明与复合物I功能障碍相关的人类疾病的发病机制。