Redox regulation of mitochondrial protein phosphatases manganese-dependent and investigation of their network interactions

Abstract

The dephosphorylation action of protein phosphatases is extremely important for the control of several cell functions. These enzymes can be found in several subcellular compartments such as the cytosol and mitochondria. Cytoplasmatic protein phosphatases are highly regulated by oxidants, however, the redox regulation of mitochondrial protein phosphatases is still unknown, even though this organelle represents one of the main sites of cellular oxidant production. Therefore, we intend to analyze the redox regulation of mitochondria protein phosphatases PP2Cm (serine/threonine protein phosphatase 2C mitochondrial) and PPTC7 (serine/threonine protein phosphatase canonical PP2C). Additionally, we sought to understand the regulation of PP2Cm and PPTC7 based on the identification and analysis of the interaction with ligands. Thus, in silico studies will be performed to identify ligands and in vitro analysis of the protein-protein interaction through pull-down assays. The activity of these protein phosphatases will be measured in the presence of oxidizing and reducing agents. From the analysis of the interaction interface between protein phosphatases and ligands, we intend to identify motifs responsible for the interaction. Therefore, we expect to elucidate the regulation of PP2Cm and PPTC7 activity, as well as the signaling pathways in which they participate, based on the identification of protein targets.(AU)