Is the mitochondrion a promising drug target in trypanosomatids?

dc.creatorRezende, Yasmin Pedra
dc.creatorBombaça, Ana Cristina Souza
dc.creatorMenna-Barreto, Rubem Figueiredo Sadok
dc.date2023-03-02T19:00:51Z
dc.date2023-03-02T19:00:51Z
dc.date2022
dc.date.accessioned2023-09-26T23:58:54Z
dc.date.available2023-09-26T23:58:54Z
dc.identifierREZENDE, Yasmin Pedra; BOMBAÇA, Ana Cristina Souza; MENNA-BARRETO, Rubem Figueiredo Sadok. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 117: e210379, p. 1 - 9, 2022.
dc.identifier0074-0206
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/57179
dc.identifier10.1590/0074-02760210379
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8896207
dc.descriptionThe trypanosomatids Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are etiological agents of important neglected tropical diseases, affecting millions of people worldwide, and the drugs available for these diseases present several limitations. Novel efficient and nontoxic drugs are necessary as an alternative to the current chemotherapy. The unique mitochondrion of trypanosomatids and its peculiar features turn this organelle a potential drug target. Several phenotypic studies describe the damage in the parasite mitochondrial ultrastructure, but the molecular target is unknown. Few reports demonstrated the electron transport system (ETS) as a target due to the high similarities to mammalian orthologues, hence ETS is not a good candidate for drug intervention. On the other hand, antioxidant enzymes, such as trypanothione reductase, and an alternative oxidase (AOX) seem to be interesting targets; however no high active inhibitors were developed up to now. Finally, due to the remarkable differences to mammalian machinery, together with the high biological importance for the parasite survival, the mitochondrial import system stands out as a very promising target in trypanosomatids. Archaic translocase of the outer membrane (ATOM) and translocase of the inner membrane (TIM) complexes, which mediate both protein and tRNA import, composed by specific subunits of these parasites, could be excellent candidates, deserving studies focused on the development of specific drugs.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFundação Oswaldo Cruz. Instituto Oswaldo Cruz.
dc.rightsopen access
dc.subjectTripanosomatídeos
dc.subjectMitocôndria
dc.subjectEstresse oxidativo
dc.subjectQuimioterapia
dc.subjectImportação de proteína mitocondrial
dc.subjectBioenergética
dc.subjectTrypanosomatids
dc.subjectMitochondrion
dc.subjectOxidative stress
dc.subjectChemotherapy
dc.subjectMitochondrial protein import
dc.subjectBioenergetics
dc.titleIs the mitochondrion a promising drug target in trypanosomatids?
dc.typeArticle


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