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.
