The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
DOI: | 10.1074/jbc.M116.772624 |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/25492 |
Resumo: | Menezes, Juliana Perrone Bezerra de. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. |
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Mittra, BidyottamSilva, Maria Fernanda LaranjeiraMiguel, Danilo CicconeMenezes, Juliana Perrone Bezerra deAndrews, Norma W2018-03-26T14:34:09Z2018-03-26T14:34:09Z2017MITTRA, B. et al. The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence. Journal of Biological Chemistry, v. 292, n. 29, p. 12324–12338, 2017.0021-9258https://www.arca.fiocruz.br/handle/icict/2549210.1074/jbc.M116.772624Menezes, Juliana Perrone Bezerra de. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.National Institutes of Health Grant R01 AI067979 (to N. W. A.).University of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USAUniversity of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USAUniversity of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USAUniversity of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USAUniversity of Maryland. Department of Cell Biology and Molecular Genetics. Maryland, USALeishmaniasis is one of the leading globally neglected diseases, affecting millions of people worldwide.Leishmaniainfection depends on the ability of insect-transmitted metacyclic promastigotes to invade mammalian hosts, differentiate into amastigotes, and replicate inside macrophages. To counter the hostile oxidative environment inside macrophages, these protozoans contain anti-oxidant systems that include iron-dependent superoxide dismutases (SODs) in mitochondria and glycosomes. Increasing evidence suggests that in addition to this protective role,Leishmaniamitochondrial SOD may also initiate H2O2-mediated redox signaling that regulates gene expression and metabolic changes associated with differentiation into virulent forms. To investigate this hypothesis, we examined the specific role of SODA, the mitochondrial SOD isoform inLeishmania amazonensisOur inability to generateL. amazonensis SODAnull mutants and the lethal phenotype observed following RNAi-mediated silencing of theTrypanosoma brucei SODAortholog suggests that SODA is essential for trypanosomatid survival.L. amazonensismetacyclic promastigotes lacking oneSODAallele failed to replicate in macrophages and were severely attenuated in their ability to generate cutaneous lesions in mice. Reduced expression of SODA also resulted in mitochondrial oxidative damage and failure ofSODA/ΔsodApromastigotes to differentiate into axenic amastigotes. SODA expression above a critical threshold was also required for the development of metacyclic promastigotes, asSODA/ΔsodAcultures were strongly depleted in this infective form and more susceptible to reactive oxygen species (ROS)-induced stress. Collectively, our data suggest that SODA promotesLeishmaniavirulence by protecting the parasites against mitochondrion-generated oxidative stress and by initiating ROS-mediated signaling mechanisms required for the differentiation of infective forms.engAmerican Society for Biochemistry and Molecular BiologyLeishmaniaDiferenciaçãoFerro superóxido dismutaseMitocôndriaSinalização redoxSuperóxido dismutase (SODLeishmaniaDifferentiationIron superoxide dismutaseMitochondriaRedox signalingSuperoxide dismutase (SOD)The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania 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/25492/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMittra B The 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dc.title.pt_BR.fl_str_mv |
The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence |
title |
The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence |
spellingShingle |
The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence Mittra, Bidyottam Leishmania Diferenciação Ferro superóxido dismutase Mitocôndria Sinalização redox Superóxido dismutase (SOD Leishmania Differentiation Iron superoxide dismutase Mitochondria Redox signaling Superoxide dismutase (SOD) |
title_short |
The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence |
title_full |
The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence |
title_fullStr |
The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence |
title_full_unstemmed |
The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence |
title_sort |
The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence |
author |
Mittra, Bidyottam |
author_facet |
Mittra, Bidyottam Silva, Maria Fernanda Laranjeira Miguel, Danilo Ciccone Menezes, Juliana Perrone Bezerra de Andrews, Norma W |
author_role |
author |
author2 |
Silva, Maria Fernanda Laranjeira Miguel, Danilo Ciccone Menezes, Juliana Perrone Bezerra de Andrews, Norma W |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Mittra, Bidyottam Silva, Maria Fernanda Laranjeira Miguel, Danilo Ciccone Menezes, Juliana Perrone Bezerra de Andrews, Norma W |
dc.subject.other.pt_BR.fl_str_mv |
Leishmania Diferenciação Ferro superóxido dismutase Mitocôndria Sinalização redox Superóxido dismutase (SOD |
topic |
Leishmania Diferenciação Ferro superóxido dismutase Mitocôndria Sinalização redox Superóxido dismutase (SOD Leishmania Differentiation Iron superoxide dismutase Mitochondria Redox signaling Superoxide dismutase (SOD) |
dc.subject.en.pt_BR.fl_str_mv |
Leishmania Differentiation Iron superoxide dismutase Mitochondria Redox signaling Superoxide dismutase (SOD) |
description |
Menezes, Juliana Perrone Bezerra de. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2018-03-26T14:34:09Z |
dc.date.available.fl_str_mv |
2018-03-26T14:34:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MITTRA, B. et al. The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence. Journal of Biological Chemistry, v. 292, n. 29, p. 12324–12338, 2017. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/25492 |
dc.identifier.issn.pt_BR.fl_str_mv |
0021-9258 |
dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M116.772624 |
identifier_str_mv |
MITTRA, B. et al. The iron-dependent mitochondrial superoxide dismutase SODA promotesLeishmania virulence. Journal of Biological Chemistry, v. 292, n. 29, p. 12324–12338, 2017. 0021-9258 10.1074/jbc.M116.772624 |
url |
https://www.arca.fiocruz.br/handle/icict/25492 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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American Society for Biochemistry and Molecular Biology |
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American Society for Biochemistry and Molecular Biology |
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