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THE DOUBLE-EDGED SWORD IN PATHOGENIC TRYPANOSOMATIDS: THE PIVOTAL ROLE OF MITOCHONDRIA IN OXIDATIVE STRESS AND BIOENERGETICS
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil
Abstract
The pathogenic trypanosomatids Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. are the causative agents of African
trypanosomiasis, Chagas disease, and leishmaniasis, respectively. These diseases are considered to be neglected tropical illnesses
that persist under conditions of poverty and are concentrated in impoverished populations in the developing world. Novel efficient
and nontoxic drugs are urgently needed as substitutes for the currently limited chemotherapy. Trypanosomatids display a single
mitochondrion with several peculiar features, such as the presence of different energetic and antioxidant enzymes and a specific
arrangement ofmitochondrialDNA(kinetoplastDNA).Due tomitochondrial differences betweenmammals and trypanosomatids,
this organelle is an excellent candidate for drug intervention. Additionally, during trypanosomatids’ life cycle, the shape and
functional plasticity of their single mitochondrion undergo profound alterations, reflecting adaptation to different environments.
In an uncoupling situation, the organelle produces high amounts of reactive oxygen species. However, these species role in parasite
biology is still controversial, involving parasite death, cell signalling, or even proliferation. Novel perspectives on trypanosomatidtargeting
chemotherapy could be developed based on better comprehension of mitochondrial oxidative regulation processes.
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