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Mitochondrial redox shuttles as novel mechanisms to regulate energy homeostasis in Trypanosoma cruzi parasites


Mitochondria are central hubs of energy metabolism, integrating vital cellular processes through signals emanated from and to this organelle. Mitochondrial redox shuttles oxidize cytosolic NADH and transfer its reduced equivalents to mitochondria, interconnecting glucose, and lipid metabolism to oxidative phosphorylation. Although mitochondrial redox shuttles were functionally identified in distinct organisms and tissues, their existence and biological significance in trypanosomatids remain largely unknown. In the context of a partnership between USP, Fiocruz-RJ and UFRJ we are initiating a systematic in silico analysis of mitochondrial redox shuttles components of both Trypanosoma cruzi and Leishmania spp. and to understand how regulation of the inter-organelle redox balance contributes to cell physiology. The goal of this proposal is to establish in São Paulo the protocols for assessment of mitochondrial redox shuttles activity in trypanosomatids, as well as to determine the metabolic and cellular consequences in Trypanosoma cruzi. The experimental approach was designed to understand how mitochondrial redox shuttles are modulated by nutrient availability, parasite life-cycle, and redox challenges, but also how mitochondrial redox shuttles contributes to cell viability, proliferation, and development. Finally, we plan to expand the impact of the visit by offering a short intensive course for graduate students, and several seminars in research Institutions in the State of São Paulo. (AU)

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