Regulation of mitochondrial respiratory complex I

线粒体呼吸复合物 I 的调节

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/8129567
• 关键词: Applications Grants; Cell Line; Cell model; Cells; Complex; Cytochrome c Reductase; Degenerative Disorder; 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（复合体I）受核和线粒体双重遗传控制，在氧化磷酸化中起核心作用。这种呼吸复合体由45个亚基组成，与人类遗传和获得性疾病有关。在之前的研究中，我们已经分离出几种缺乏复合物I组装和线粒体功能的细胞系。我们进一步确定了一个假定的蛋白因子，其过表达与复合体I组装的恢复有关。该提案的具体目标是：1)确定我们鉴定的蛋白质是否为复合体I组装因子2)开发一种分离基因的遗传方法，可以补偿复合体I基因突变引起的线粒体缺陷。该研究的成功将有助于我们了解呼吸复合体I的组装和功能调控，并为开发复合体I缺乏症的治疗方法提供有用的线索。

项目成果

Respiratory supercomplexes: plasticity and implications.

• DOI: 10.2741/4327
• 发表时间: 2015-01-01
• 期刊: Frontiers in bioscience (Landmark edition)
• 作者: Porras CA;Bai Y
• 通讯作者: Bai Y

Respiratory supercomplexes: structure, function and assembly.

• DOI: 10.1007/s13238-013-3032-y
• 发表时间: 2013-08
• 期刊: Protein & cell
• 影响因子: 21.1
• 作者: Vartak R;Porras CA;Bai Y
• 通讯作者: Bai Y

An update on complex I assembly: the assembly of players.

• DOI: 10.1007/s10863-014-9564-x
• 发表时间: 2014-08
• 期刊: JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
• 影响因子: 3
• 作者: Vartak, Rasika S.;Semwal, Manpreet Kaur;Bai, Yidong
• 通讯作者: Bai, Yidong

Mitochondrial common deletion, a potential biomarker for cancer occurrence, is selected against in cancer background: a meta-analysis of 38 studies.

线粒体常见缺失是癌症发生的潜在生物标志物，在癌症背景下被选择：对 38 项研究的荟萃分析

• DOI: 10.1371/journal.pone.0067953
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Nie H;Shu H;Vartak R;Milstein AC;Mo Y;Hu X;Fang H;Shen L;Ding Z;Lu J;Bai Y
• 通讯作者: Bai Y