Is the mitochondrion a promising drug target in trypanosomatids?
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 necess...
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
2022-02-01
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| Series: | Memorias do Instituto Oswaldo Cruz |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762022000100850&tlng=en |
| _version_ | 1797721303627595776 |
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| author | Yasmin Pedra-Rezende Ana Cristina Souza Bombaça Rubem Figueiredo Sadok Menna-Barreto/ |
| author_facet | Yasmin Pedra-Rezende Ana Cristina Souza Bombaça Rubem Figueiredo Sadok Menna-Barreto/ |
| author_sort | Yasmin Pedra-Rezende |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T09:31:32Z |
| format | Article |
| id | doaj.art-d13c8d612bfc448791c57b5a05a4abe9 |
| institution | Directory Open Access Journal |
| issn | 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T09:31:32Z |
| publishDate | 2022-02-01 |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-d13c8d612bfc448791c57b5a05a4abe92023-09-02T13:54:13ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-80602022-02-0111710.1590/0074-02760210379Is the mitochondrion a promising drug target in trypanosomatids?Yasmin Pedra-RezendeAna Cristina Souza BombaçaRubem Figueiredo Sadok Menna-Barreto/https://orcid.org/0000-0002-1352-0641The 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762022000100850&tlng=entrypanosomatidsmitochondrionoxidative stresschemotherapymitochondrial protein importbioenergetics |
| spellingShingle | Yasmin Pedra-Rezende Ana Cristina Souza Bombaça Rubem Figueiredo Sadok Menna-Barreto/ Is the mitochondrion a promising drug target in trypanosomatids? Memorias do Instituto Oswaldo Cruz trypanosomatids mitochondrion oxidative stress chemotherapy mitochondrial protein import bioenergetics |
| title | Is the mitochondrion a promising drug target in trypanosomatids? |
| title_full | Is the mitochondrion a promising drug target in trypanosomatids? |
| title_fullStr | Is the mitochondrion a promising drug target in trypanosomatids? |
| title_full_unstemmed | Is the mitochondrion a promising drug target in trypanosomatids? |
| title_short | Is the mitochondrion a promising drug target in trypanosomatids? |
| title_sort | is the mitochondrion a promising drug target in trypanosomatids |
| topic | trypanosomatids mitochondrion oxidative stress chemotherapy mitochondrial protein import bioenergetics |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762022000100850&tlng=en |
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