Characterization and role of the 3-methylglutaconyl coenzyme A hidratase in Trypanosoma brucei

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dc.citation.volume214]
dc.contributor.authorDe Lima-Stein, Mariana Leão [UNIFESP]
dc.contributor.authorIcimoto, Marcelo Yudi [UNIFESP]
dc.contributor.authorLevatti, Erica Valadares de Castro [UNIFESP]
dc.contributor.authorOliveira, Vitor [UNIFESP]
dc.contributor.authorStraus, Anita Hilda [UNIFESP]
dc.contributor.authorSchenkman, Sergio [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.coverageAmsterdam
dc.date.accessioned2020-06-26T16:30:42Z
dc.date.available2020-06-26T16:30:42Z
dc.date.issued2017
dc.description.abstractTrypanosoma brucei, the agent of African Trypanosomiasis, is a flagellated protozoan parasite that develops in tsetse flies and in the blood of various mammals. The parasite acquires nutrients such as sugars, lipids and amino acids from their hosts. Amino acids are used to generate energy and for protein and lipid synthesis. However, it is still unknown how T. brucei catabolizes most of the acquired amino acids. Here we explored the role of an enzyme of the leucine catabolism, the 3-methylglutaconyl-Coenzyme A hydratase (3-MGCoA-H). It catalyzes the hydration of 3-methylglutaconyl-Coenzyme A (3-MGCoA) into 3-hydroxymethylglutaryl-Coenzyme A (3-HMGCoA). We found that 3-MGCoA-H localizes in the mitochondria) matrix and is expressed in both insect and mammalian bloodstream forms of the parasite. The depletion of 3-MGCoA-H by RNA interference affected minimally the proliferation of both forms. However, an excess of leucine in the culture medium caused growth defects in cells depleted of 3-MGCoA-H, which could be reestablished by mevalonate, a precursor of isoprenoids and steroids. Indeed, procyclics depleted of the 3-MGCoA-H presented reduced levels of synthesized steroids relative to cholesterol that is scavenged by the parasite, and these levels were also reestablished by mevalonate. These results suggest that accumulation of leucine catabolites could affect the level of mevalonate and consequently inhibit the sterol biosynthesis, required for T. brucei growth. (C) 2017 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp[Univ Fed Sao Paulo, Dept Biofis, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipIDFAPESP: 11/51973-3pt
dc.description.sponsorshipIDFAPESP: 2015/22031-0pt
dc.description.sponsorshipIDCNPq: 445655/2014-3pt
dc.description.sponsorshipIDCNPq: 306815/2015-0pt
dc.format.extent36-46
dc.identifierhttps://dx.doi.org/10.1016/j.molbiopara.2017.03.007]
dc.identifier.citationMolecular And Biochemical Parasitology. Amsterdam, v. 214, p. 36-46, 2017.
dc.identifier.doi10.1016/j.molbiopara.2017.03.007
dc.identifier.issn0166-6851
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53704
dc.identifier.wosWOS:000404795200005
dc.language.isoeng
dc.publisherElsevier Science Bv
dc.relation.ispartofMolecular And Biochemical Parasitology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectTrypanosoma bruceien
dc.subjectLeucineen
dc.subject3-methylglutaconyl CoAen
dc.subjectRNAien
dc.subjectErgosterolen
dc.subjectMevalonateen
dc.titleCharacterization and role of the 3-methylglutaconyl coenzyme A hidratase in Trypanosoma bruceien
dc.typeinfo:eu-repo/semantics/article
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