A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression

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dc.citation.titleJournal of Biological Chemistry (JBC)es
dc.creatorPagura, Lucas
dc.creatorTevere, Evelyn
dc.creatorMerli, Marcelo Luciano
dc.creatorCricco, Julia Alejandra
dc.date.accessioned2021-04-12T19:14:00Z
dc.date.available2021-04-12T19:14:00Z
dc.date.issued2020-07-23
dc.descriptionHeme is an essential cofactor for many biological processes in aerobic organisms, which can synthesize it de novo through a conserved pathway. Trypanosoma cruzi, the etiological agent of Chagas disease, as well as other trypanosomatids relevant to human health, are heme auxotrophs, meaning they must import it from their mammalian hosts or insect vectors. However, how these species import and regulate heme levels is not fully defined yet. It is known that the membrane protein TcHTE is involved in T. cruzi heme transport, although its specific role remains unclear. In the present work, we studied endogenous TcHTE in the different life cycle stages of the parasite to gain insight into its function in heme transport and homeostasis. We have confirmed that TcHTE is predominantly detected in repli cative stages (epimastigote and amastigote), in which heme transport activity was previously validated. We also showed that in epimastigotes, TcHTE protein and mRNA levels decrease in response to increments in heme concentration, confirming it as a member of the heme response gene family. Finally, we demon strated that T. cruzi epimastigotes can sense intracellular heme by an unknown mechanism and regulate heme transport to adapt to changing conditions. Based on these results, we pro pose a model in which T. cruzi senses intracellular heme and regulates heme transport activity by adjusting the expression of TcHTE. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding of a critical pathway for T. cruzi biology allowing the identification of novel and essential proteins.es
dc.descriptionThis is a post-peer-review, pre-copyedit version of an article published in Journal of Biological Chemistry (JBC). The final authenticated version is available online at: https://doi.org/10.1074/jbc.ra120.014574
dc.description.filFil: Pagura, Lucas. Universidad Nacional de Rosario. Facultad de Ciencias Bioquƭmicas y FarmacƩuticas. Instituto de Biologƭa Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Tevere, Evelyn. Universidad Nacional de Rosario. Facultad de Ciencias Bioquƭmicas y FarmacƩuticas. Instituto de Biologƭa Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Merli, Marcelo Luciano. Universidad Nacional de Rosario. Facultad de Ciencias Bioquƭmicas y FarmacƩuticas. Instituto de Biologƭa Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquƭmicas y FarmacƩuticas. Instituto de Biologƭa Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias BioquĆ­micas y FarmacĆ©uticas. Departamento de QuĆ­mica BiolĆ³gica. Ɓrea BiofĆ­sica; Argentina.es
dc.description.sponsorshipUK Research and Innovation: Global Challenges Research Fund under grant agreement ā€œA Global Network for Neglected Tropical Diseasesā€ Grant MR/P027989/1es
dc.description.sponsorshipAgencia Nacional de PromociĆ³n CientĆ­fica y TecnolĆ³gica (ANPCyT): Grant PICT 2015-2437 y PICT 2015ā€“2437es
dc.formatapplication/pdf
dc.format.extent13202ā€“13212es
dc.identifier.issn1083-351Xes
dc.identifier.urihttp://hdl.handle.net/2133/20478
dc.language.isoenges
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes
dc.relation.publisherversionhttps://www.jbc.org/article/S0021-9258(17)50037-X/fulltextes
dc.relation.publisherversionhttps://doi.org/10.1074/jbc.ra120.014574es
dc.rightsopenAccesses
dc.rights.holderPagura, Lucases
dc.rights.holderTevere, Evelynes
dc.rights.holderMerli, Marcelo Lucianoes
dc.rights.holderCricco, Julia Alejandraes
dc.rights.holderUniversidad Nacional de Rosario
dc.rights.textAttribution 4.0 International (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectTrypanosoma cruzies
dc.subjectChagas Diseasees
dc.subjectHeme Responsive Genees
dc.subjectHeme Transportes
dc.subjectHomeostasises
dc.subjectParasiteses
dc.titleA new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expressiones
dc.typearticle
dc.typeartĆ­culo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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