Biochemical regulation of mitochondrial uncoupling protein 3

描述（由申请人提供）：解偶联蛋白（UCP）是线粒体！跨物种保守的内膜阴离子载体蛋白。UCP通过主要底物乙酰辅酶A的代谢消除电子传递链产生的质子梯度。UCP具有多种功能，包括非颤抖性产热、消耗过量底物和减少活性氧。尽管这些蛋白质执行各种功能，但没有发现其他蛋白质与任何UCP直接相互作用。最近的酵母双杂交实验的结果表明，蛋白δ 2，4，δ 3，5二烯酰辅酶A异构酶（DDI）结合解偶联蛋白3（UCPS）的亲水环1，2和4。当这些蛋白质在培养的哺乳动物细胞中过表达时，通过免疫共沉淀也观察到这种相互作用。蛋白质DDI是β氧化途径的辅助蛋白质，其将不饱和脂肪酸的奇数双键移动到偶数位置，以使其准备用于催化成乙酰辅酶A。本项目将利用生物化学、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性质。更具体地说，我们将绘制UCP 3：DDI相互作用结构域，并确定蛋白质影响其他功能的程度。这项研究与公共卫生的相关性：身体如何利用能量和分解脂肪在许多疾病中起着重要作用。这项研究将为代谢紊乱（如糖尿病和肥胖）之间的联系提供新的见解，并可能最终为患者带来更先进的治疗选择。

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.