Biophysical and biochemical studies of the mitochondrial uncoupling proteins

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Membrane proteins are incorporated in and/or interact with the cell membranes.  These proteins are responsible for a variety of biological functions crucial for the maintenance of life in living organisms, such as transport of ions and nutrients across cell membranes and communication in between cells through facilitating the transfer of electrochemical signals.  Understanding the details of these functions at the molecular level will significantly improve the insight into the life processes and effectively contribute to several areas of human health research.  Mitochondrial uncoupling proteins (UCPs) are the focus of this research program. These intriguing proteins are located in the inner membranes of the mitochondria of certain animal and plant tissues, and uncouple the respiration from the ATP synthesis in cells. Only limited information has been documented on the structures of UCPs in membranes.  Apart from the well-established role of one of these proteins, UCP1, in regulating the temperature in the body of young mammals, the detailed physiological roles of other UCPs are not clearly understood. Possible roles of UCPs in response to oxidative stress, lipid peroxidation, diabetes, fever, inflammatory processes and nervous system protection have been suggested. Consequently, detailed studies of UCPs and their diverse and apparently unrelated physiological roles is significant in understanding the molecular biology of certain cellular systems that are involved in regulation of vital biochemical processes in mammals.   The proposed research program will focus on exploring the membrane structure of the uncoupling proteins, their interaction with and folding in membranes, and the details of the ion transport mechanism as their major biological function.  The proposed research program is original and interdisciplinary, and combines spectroscopic methods of structural analysis with synthetic, electrophysiological, thermochemical and molecular modeling techniques in an integrated study to explore the biophysical basis of the structure-function relationships in the uncoupling proteins.