Use este identificador para citar ou linkar para este item:
https://www.arca.fiocruz.br/handle/icict/57179
Tipo de documento
ArtigoDireito Autoral
Acesso aberto
Coleções
- IOC - Artigos de Periódicos [12502]
Metadata
Mostrar registro completo
IS THE MITOCHONDRION A PROMISING DRUG TARGET IN TRYPANOSOMATIDS?
Mitocôndria
Estresse oxidativo
Quimioterapia
Importação de proteína mitocondrial
Bioenergética
Mitochondrion
Oxidative stress
Chemotherapy
Mitochondrial protein import
Bioenergetics
Afiliação
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.
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.
Resumo em Inglês
The 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.
Palavras-chave
TripanosomatídeosMitocôndria
Estresse oxidativo
Quimioterapia
Importação de proteína mitocondrial
Bioenergética
Palavras-chave em inglês
TrypanosomatidsMitochondrion
Oxidative stress
Chemotherapy
Mitochondrial protein import
Bioenergetics
Compartilhar