Biochemical regulation of mitochondrial uncoupling protein 3

线粒体解偶联蛋白3的生化调控

• 批准号: 7873029
• 负责人: Monte Alexander Kenaston
• 金额: $ 1.91万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2010-12-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7873029
• 关键词: ATP Synthesis Pathway; Affect; American Indians; Anions; Binding; Biochemical; Biological; Biological Assay; Cardiac Myoblasts; Carrier Proteins; Catalysis; Cell Line; Cells; Co-Immunoprecipitations; Data; Diabetes Mellitus; Disease; Electron Transport; Environment; Epitopes; Expenditure; Fatty acid glycerol esters; Flow Cytometry; Genes; Genetic; Heart; Heating; Hispanics; Human; Immunoprecipitation; In Vitro; Incidence; Inner mitochondrial membrane; Lead; Life Style; Link; Mammalian Cell; Maps; Medical; Membrane; Membrane Potentials; Metabolic Diseases; Metabolism; Methodology; Minority; Mitochondria; Molecular; Molecular Biology; Mus; Mutate; Native Americans; Nature; Nutritional status; Obesity; Pathway interactions; Patients; Play; Population; Positioning Attribute; Protein Binding; Proteins; Protons; Public Health; Reactive Oxygen Species; Regulation; Research; Shivering; Testing; Thermogenesis; Unsaturated Fatty Acids; Yeasts; delta protein; delta(3,5),delta(2,4)-dienoyl-CoA isomerase; energy balance; fatty acid metabolism; fatty acid oxidation; in vivo; insight; loss of function; mitochondrial membrane; mitochondrial uncoupling protein 3; mutant; overexpression; oxidation; pi bond; research study; stem; wasting; yeast two hybrid system

DESCRIPTION (provided by applicant): Uncoupling proteins (UCPs) are mitochondria! inner membrane anion carrier proteins that are well conserved across species. UCPs dissipate the proton gradient that is generated by the electron transport chain through the metabolism of the primary substrate acetyl Co-A. UCPs have diverse functions including non-shivering thermogenesis, expenditure of excess substrates, and reduction of reactive oxygen species. Despite the various functions performed by these proteins, no other protein has been found to directly interact with any UCP. Recent results of a yeast-two hybrid experiment indicate that the protein delta 2,4, delta 3,5 dienoyl-CoA isomerase (DDI) binds hydrophilic loops 1, 2, and 4 of uncoupling protein 3 (UCPS). This interaction was also observed via co-immunoprecipitation when these proteins were overexpressed in cultured mammalian cells. The protein DDI is an auxiliary protein of the beta oxidation pathway that moves odd-numbered double bonds of unsaturated fatty acids to even-numbered positions in order to prepare them for catalysis into acetyl Co-A. This project will explore the nature of this protein interaction using biochemical, cell biological, and molecular biology methodologies. More specifically, we will map the UCP3:DDI interacting domains and ascertain the extent to which the proteins influence the functions of the other. Relevance of this research to public health: Abnormalities in how the body uses energy and breaks down fat play an important part in numerous diseases. This research will provide new insight on the link between metabolic disorders, such as diabetes and obesity, and may ultimately lead to more advanced treatment options for patients.

描述(申请人提供)：解偶联蛋白(UCP)是线粒体！内膜负离子载体蛋白，在物种间保存良好。UCP通过初级底物乙酰Co-A的新陈代谢来消散电子传输链产生的质子梯度。UCPs具有多种功能，包括不颤抖生热、消耗多余底物和减少活性氧物种。尽管这些蛋白质具有不同的功能，但还没有发现其他蛋白质与任何UCP直接相互作用。酵母双杂交实验的最新结果表明，Delta2，4，Delta3，5二烯酰辅酶A异构酶(DDI)与解偶联蛋白3(UCPs)的亲水环1，2和4结合。当这些蛋白质在培养的哺乳动物细胞中过表达时，这种相互作用也通过免疫共沉淀观察到。蛋白质DDI是β氧化途径的一种辅助蛋白质，它将不饱和脂肪酸的奇数双键移动到偶数位置，以便为催化合成乙酰辅酶A做准备。这个项目将使用生化、细胞生物学和分子生物学方法来探索这种蛋白质相互作用的本质。更具体地说，我们将绘制UCP3：DDI相互作用结构域的图谱，并确定这些蛋白质影响另一个蛋白质功能的程度。这项研究与公共健康的相关性：身体利用能量和分解脂肪的异常在许多疾病中发挥着重要作用。这项研究将为糖尿病和肥胖症等代谢紊乱之间的联系提供新的见解，并最终可能为患者带来更先进的治疗选择。