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Structural and functional characterization of mitochondrial protein phosphatases by redox metabolism and their role in cell biology

Abstract

Protein phosphatases act in a coordinated way on cell signaling pathways that play a role in various physiological and pathological processes. These enzymes are found in several cellular compartments, such as cytosol and mitochondria, and the regulation of the activity of these enzymes is central to a better understanding of these processes. Although knowledge about mitochondrial protein phosphatases is very limited, it is known that some of these regulate cell metabolism, glucose homeostasis, insulin release and participate in the pathogenesis of numerous diseases. Cytoplasmic protein phosphatases are highly regulated by oxidants, however redox regulation of mitochondrial protein phosphatases is still unknown, moreover this organelle represents one of the major sites of cellular oxidant (ROS) production. Since cellular oxidants play an important role in modulating the enzyme activity and cellular processes, we postulate that the redox regulation of mitochondrial protein phosphatases should be unique and with direct implications for signaling, metabolism and cellular functions. Thus, this project aims to investigate the mechanism of redox regulation of mitochondrial protein phosphatases, through a functional and structural approach. As a result, we expected the identification of unique mechanisms of redox regulation of these enzymes. This will greatly contribute to a better understanding of the phosphatase inhibition by oxidation and the development of therapeutic tools using mitochondrial phosphatases as a target for the treatment of important human pathologies, such as diabetes and cancer. (AU)

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