Regulation of mitochondrial respiratory complex I

线粒体呼吸复合物 I 的调节

基本信息

批准号：
8129567
负责人：
Yidong Bai
金额：
$ 21.83万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-16 至 2014-07-31
项目状态：
已结题

项目摘要

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）：在双重遗传控制，核和线粒体下的哺乳动物NADH脱氢酶（复杂I）在氧化磷酸化中起着核心作用。这种呼吸复合物由45个亚基组成，并与人类遗传和获得性疾病有关。在先前的研究中，我们分离了几个细胞系在复合I组装和线粒体功能中缺乏。我们进一步确定了一个推定的蛋白质因子，其过表达与恢复的复合物I组装相关。该提案的具体目的是：1）确定我们确定的蛋白质是否是复杂的I组装因子2）开发一种遗传方法，以对可以补偿由复杂I基因突变引起的线粒体缺乏症来补偿分离的基因。该提案的成功将有助于我们了解呼吸复合物I的组装和功能的调节，并为开发用于复杂I缺乏症的治疗方法提供了有用的线索。公共卫生相关性：我们提交此赠款申请，重点是了解线粒体呼吸道复合物的功能和调节。特别是，我们将开发一种新型方法来隔离调节线粒体功能的重要蛋白质因子。该项目的成功将提高我们对线粒体功能的理解，并阐明与复杂I功能障碍相关的人类疾病的发病机理。