University of California, San Diego (UCSD)

Beyond Insulin Secretion: The Role of Mitochondrial Phosphatase PTPMT1 in Diabetes

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Mitochondria are membrane-bound organelle found in animal and plant cells, providing the power source for cellular activities. Disorders of mitochondrial function lead to a number of diseases, such as obesity and diabetes. Reversible modification of proteins by phosphorylation has been underestimated as a means of regulation within mitochondria. Recently a novel mitochondrial phosphatase, PTPMT1, has been found to regulate the insulin secretion in pancreatic β-cells. However, the mechanism of PTPMT1 action is not clear. The proposed study will focus on generate mice deficient of PTPMT1 and characterizing their phenotypes. A series of combined systemic and biochemical approaches will be utilized to identify the substrates. A putative inhibitor of PTPMT1 that was discovered from a chemical library will further analyzed. Successful completion of this project would enable us to better understand the role of reversible phosphorylation in regulating mitochondrial function and energy metabolism, and may provide a new therapeutic intervention for metabolic disorders.