A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/18191 |
Resumo: | National Institutes of Health grant RO1 AI067979 to NWA. MFLS was supported by the CAPES Ciência sem Fronteiras fellowship 10686/13-4. |
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Mittra, BidyottamSilva, Maria Fernanda LaranjeiraMenezes, Juliana Perrone Bezerra deJensen, JenniferMichailowsky, VladimirAndrews, Norma W2017-03-28T17:55:49Z2017-03-28T17:55:49Z2016MITTRA, B. et al. A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence. Plos Pathogens, v. 12, n. 1, p. e1005340, 2016.1553-7366https://www.arca.fiocruz.br/handle/icict/1819110.1371/journal.ppat.1005340National Institutes of Health grant RO1 AI067979 to NWA. MFLS was supported by the CAPES Ciência sem Fronteiras fellowship 10686/13-4.University of Maryland, College Park. Department of Cell Biology and Molecular Genetics. Maryland, USAUniversity of Maryland, College Park. Department of Cell Biology and Molecular Genetics. Maryland, USAUniversity of Maryland, College Park. Department of Cell Biology and Molecular Genetics. Maryland, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilUniversity of Maryland, College Park. Department of Cell Biology and Molecular Genetics. Maryland, USAUniversity of Maryland, College Park. Department of Cell Biology and Molecular Genetics. Maryland, USA / Universidade Federal do Ceará. Faculdade de Medicina. Setor Parasitologia. Fortaleza, CE, BrasilUniversity of Maryland, College Park. Department of Cell Biology and Molecular Genetics. Maryland, USAIron, an essential co-factor of respiratory chain proteins, is critical for mitochondrial function and maintenance of its redox balance. We previously reported a role for iron uptake in differentiation of Leishmania amazonensis into virulent amastigotes, by a mechanism that involves reactive oxygen species (ROS) production and is independent of the classical pH and temperature cues. Iron import into mitochondria was proposed to be essential for this process, but evidence supporting this hypothesis was lacking because the Leishmania mitochondrial iron transporter was unknown. Here we describe MIT1, a homolog of the mitochondrial iron importer genes mrs3 (yeast) and mitoferrin-1 (human) that is highly conserved among trypanosomatids. MIT1 expression was essential for the survival of Trypanosoma brucei procyclic but not bloodstream forms, which lack functional respiratory complexes. L. amazonensis LMIT1 null mutants could not be generated, suggesting that this mitochondrial iron importer is essential for promastigote viability. Promastigotes lacking one LMIT1 allele (LMIT1/Δlmit1) showed growth defects and were more susceptible to ROS toxicity, consistent with the role of iron as the essential co-factor of trypanosomatid mitochondrial superoxide dismutases. LMIT1/Δlmit1 metacyclic promastigotes were unable to replicate as intracellular amastigotes after infecting macrophages or cause cutaneous lesions in mice. When induced to differentiate axenically into amastigotes, LMIT1/Δlmit1 showed strong defects in iron content and function of mitochondria, were unable to upregulate the ROS-regulatory enzyme FeSOD, and showed mitochondrial changes suggestive of redox imbalance. Our results demonstrate the importance of mitochondrial iron uptake in trypanosomatid parasites, and highlight the role of LMIT1 in the iron-regulated process that orchestrates differentiation of L. amazonensis into infective amastigotes.engPublic Library of ScienceLeishmaniaLeishmanioseSeqüência de aminoácidosModelos de doençasMicroscopia eletrônicaMitocôndriaVirulênciaLeishmaniaLeishmaniasisAmino acid sequenceDisease models, animalMicroscopy, electronMitochondriaVirulenceA Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulenceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/18191/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMittra B A 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| dc.title.pt_BR.fl_str_mv |
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence |
| title |
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence |
| spellingShingle |
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence Mittra, Bidyottam Leishmania Leishmaniose Seqüência de aminoácidos Modelos de doenças Microscopia eletrônica Mitocôndria Virulência Leishmania Leishmaniasis Amino acid sequence Disease models, animal Microscopy, electron Mitochondria Virulence |
| title_short |
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence |
| title_full |
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence |
| title_fullStr |
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence |
| title_full_unstemmed |
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence |
| title_sort |
A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence |
| author |
Mittra, Bidyottam |
| author_facet |
Mittra, Bidyottam Silva, Maria Fernanda Laranjeira Menezes, Juliana Perrone Bezerra de Jensen, Jennifer Michailowsky, Vladimir Andrews, Norma W |
| author_role |
author |
| author2 |
Silva, Maria Fernanda Laranjeira Menezes, Juliana Perrone Bezerra de Jensen, Jennifer Michailowsky, Vladimir Andrews, Norma W |
| author2_role |
author author author author author |
| dc.contributor.author.fl_str_mv |
Mittra, Bidyottam Silva, Maria Fernanda Laranjeira Menezes, Juliana Perrone Bezerra de Jensen, Jennifer Michailowsky, Vladimir Andrews, Norma W |
| dc.subject.other.pt_BR.fl_str_mv |
Leishmania Leishmaniose Seqüência de aminoácidos Modelos de doenças Microscopia eletrônica Mitocôndria Virulência |
| topic |
Leishmania Leishmaniose Seqüência de aminoácidos Modelos de doenças Microscopia eletrônica Mitocôndria Virulência Leishmania Leishmaniasis Amino acid sequence Disease models, animal Microscopy, electron Mitochondria Virulence |
| dc.subject.en.pt_BR.fl_str_mv |
Leishmania Leishmaniasis Amino acid sequence Disease models, animal Microscopy, electron Mitochondria Virulence |
| description |
National Institutes of Health grant RO1 AI067979 to NWA. MFLS was supported by the CAPES Ciência sem Fronteiras fellowship 10686/13-4. |
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2016 |
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2016 |
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2017-03-28T17:55:49Z |
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2017-03-28T17:55:49Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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MITTRA, B. et al. A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence. Plos Pathogens, v. 12, n. 1, p. e1005340, 2016. |
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https://www.arca.fiocruz.br/handle/icict/18191 |
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1553-7366 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.ppat.1005340 |
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MITTRA, B. et al. A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence. Plos Pathogens, v. 12, n. 1, p. e1005340, 2016. 1553-7366 10.1371/journal.ppat.1005340 |
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