Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication

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dc.citation.titleBiochemical Journales
dc.citation.volume474(14)es
dc.creatorMerli, Marcelo Luciano
dc.creatorCirulli, Brenda Analía
dc.creatorMenendez Bravo, Simón M.
dc.creatorCricco, Julia Alejandra
dc.date.accessioned2020-06-09T13:54:38Z
dc.date.available2020-06-09T13:54:38Z
dc.date.issued2017-06-27
dc.descriptionTrypanosoma cruzi, the causative agent of Chagas disease, presents a complex life cycle and adapts its metabolism to nutrients’ availability. Although T. cruzi is an aerobic organism, it does not produce heme. This cofactor is acquired from the host and is distributed and inserted into different heme-proteins such as respiratory complexes in the parasite's mitochondrion. It has been proposed that T. cruzi's energy metabolism relies on a branched respiratory chain with a cytochrome c oxidase-type aa3 (CcO) as the main terminal oxidase. Heme A, the cofactor for all eukaryotic CcO, is synthesized via two sequential enzymatic reactions catalyzed by heme O synthase (HOS) and heme A synthase (HAS). Previously, TcCox10 and TcCox15 (Trypanosoma cruzi Cox10 and Cox15 proteins) were identified in T. cruzi. They presented HOS and HAS activity, respectively, when they were expressed in yeast. Here, we present the first characterization of TcCox15 in T. cruzi, confirming its role as HAS. It was differentially detected in the different T. cruzi stages, being more abundant in the replicative forms. This regulation could reflect the necessity of more heme A synthesis, and therefore more CcO activity at the replicative stages. Overexpression of a non-functional mutant caused a reduction in heme A content. Moreover, our results clearly showed that this hindrance in the heme A synthesis provoked a reduction on CcO activity and, in consequence, an impairment on T. cruzi survival, proliferation and infectivity. This evidence supports that T. cruzi depends on the respiratory chain activity along its life cycle, being CcO an essential terminal oxidase.es
dc.description.filFil: Merli, Marcelo Luciano. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Cirulli, Brenda Analía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Menéndez-Bravo; Simón M. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.filFil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.es
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET): grant no. PIP 2013-2015 0667es
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): grant no. PICT 2010-2012 1992es
dc.formatapplication/pdf
dc.format.extent2315–2332es
dc.identifier.issn0264-6021es
dc.identifier.urihttp://hdl.handle.net/2133/18327
dc.language.isoenges
dc.publisherPortland Presses
dc.relation.publisherversionhttps://doi.org/10.1042/BCJ20170084es
dc.relation.publisherversionhttps://portlandpress.com/biochemj/article/474/14/2315/49473/Heme-A-synthesis-and-CcO-activity-are-essentiales
dc.rightsopenAccesses
dc.rights.holderMerli, Marcelo Lucianoes
dc.rights.holderCirulli, Brenda Analíaes
dc.rights.holderMenéndez-Bravo; Simón M.es
dc.rights.holderCricco, Julia Alejandraes
dc.rights.holderUniversidad Nacional de Rosarioes
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectChagas diseasees
dc.subjectcomplex IVes
dc.subjectheme Aes
dc.subjectheme A synthasees
dc.subjecttrypanosomeses
dc.titleHeme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replicationes
dc.typearticle
dc.typeartículo
dc.typeacceptedVersion
dc.type.collectionarticulo
dc.type.versionacceptedVersiones

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