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

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dc.creator Pagura, Lucas
dc.creator Tevere, Evelyn
dc.creator Merli, Marcelo Luciano
dc.creator Cricco, Julia Alejandra
dc.date.accessioned 2021-04-12T19:14:00Z
dc.date.available 2021-04-12T19:14:00Z
dc.date.issued 2020-07-23
dc.identifier.issn 1083-351X es
dc.identifier.uri http://hdl.handle.net/2133/20478
dc.description Heme 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.description This 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.sponsorship UK Research and Innovation: Global Challenges Research Fund under grant agreement “A Global Network for Neglected Tropical Diseases” Grant MR/P027989/1 es
dc.description.sponsorship Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT): Grant PICT 2015-2437 y PICT 2015–2437 es
dc.format application/pdf
dc.format.extent 13202–13212 es
dc.language.iso eng es
dc.publisher American Society for Biochemistry and Molecular Biology es
dc.rights openAccess es
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ *
dc.subject Trypanosoma cruzi es
dc.subject Chagas Disease es
dc.subject Heme Responsive Gene es
dc.subject Heme Transport es
dc.subject Homeostasis es
dc.subject Parasites es
dc.title A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression es
dc.type article
dc.type artículo
dc.type publishedVersion
dc.rights.holder Pagura, Lucas es
dc.rights.holder Tevere, Evelyn es
dc.rights.holder Merli, Marcelo Luciano es
dc.rights.holder Cricco, Julia Alejandra es
dc.rights.holder Universidad Nacional de Rosario
dc.relation.publisherversion https://www.jbc.org/article/S0021-9258(17)50037-X/fulltext es
dc.relation.publisherversion https://doi.org/10.1074/jbc.ra120.014574 es
dc.rights.text Attribution 4.0 International (CC BY 4.0) es
dc.citation.title Journal of Biological Chemistry (JBC) es
dc.description.fil Fil: Pagura, Lucas. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. es
dc.description.fil Fil: Tevere, Evelyn. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. es
dc.description.fil Fil: 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.fil Fil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. es
dc.description.fil Fil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina. es
dc.type.collection articulo
dc.type.version publishedVersion es


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