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（由申请人提供）：解耦蛋白（UCP）是线粒体！内膜阴离子载体蛋白在物种之间均能保守。 UCPS散发了通过主要底物乙酰基CO-A的代谢产生的质子梯度，该质子梯度是由电子传输链产生的。 UCP具有多种功能，包括非动荡的热发生，过量底物的支出以及活性氧的减少。尽管这些蛋白质具有各种功能，但尚未发现其他蛋白质直接与任何UCP相互作用。酵母 - 两种杂化实验的最新结果表明，蛋白质delta 2,4，三角洲3,5二氧二氧二氧化二氧甲酸异构酶（DDI）结合了解偶联蛋白3（UCPS）的亲水环1、2和4。当这些蛋白在培养的哺乳动物细胞中过表达时，还通过共免疫沉淀观察到这种相互作用。蛋白质DDI是β氧化途径的辅助蛋白，它将不饱和脂肪酸的奇数双键移至偶数位置，以便将其催化为乙酰co-A。该项目将使用生化，细胞生物学和分子生物学方法探索这种蛋白质相互作用的性质。更具体地说，我们将映射UCP3：DDI相互作用域，并确定蛋白质影响另一个功能的程度。这项研究与公共卫生的相关性：人体如何利用能量和分解脂肪的异常在许多疾病中起着重要的作用。这项研究将为糖尿病和肥胖等代谢疾病之间的联系提供新的见解，并最终可能导致患者更高级的治疗选择。