TcHRG plays a central role in orchestrating heme uptake in Trypanosoma cruzi epimastigotes

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dc.citation.titleThe FEBS Journal
dc.contributor.orcidhttps://orcid.org/0000-0001-9215-5015
dc.contributor.orcidhttps://orcid.org/0000-0002-8982-3489
dc.contributor.orcidhttps://orcid.org/0000-0002-9144-287X
dc.contributor.orcidhttps://orcid.org/0000-0002-8993-3880
dc.creatorTevere, Evelyn
dc.creatorDi Capua, Cecilia Beatriz
dc.creatorChasen, Nathan Michael
dc.creatorEtheridge, Ronald Drew
dc.creatorCricco, Julia Alejandra
dc.date.accessioned2024-10-29T14:12:00Z
dc.date.available2024-10-29T14:12:00Z
dc.date.issued2023-04-05
dc.description.abstractTrypanosoma cruzi, a heme auxotrophic parasite, can control intracellular heme content by modulating TcHRG expression when a free heme source is added to axenic culture. Herein, we explore the role of TcHRG protein in regulating the uptake of heme derived from hemoglobin in epimastigotes. It was found that the parasite’s endogenous TcHRG (protein and mRNA) responds similarly to bound (hemoglobin) and free (hemin) heme. Additionally, the overexpression of TcHRG leads to an increase in intracellular heme content. The localization of TcHRG is also not affected in parasites supplemented with hemoglobin as the sole heme source. Endocytic null epimastigotes do not show a significant difference in growth profile, intracellular heme content and TcHRG protein accumulation compared to WT when feeding with hemoglobin or hemin as a source of heme. These results suggest that the uptake of hemoglobin-derived heme likely occurs through extracellular proteolysis of hemoglobin via the flagellar pocket, and this process is governed by TcHRG. In sum, T. cruzi epimastigotes controls heme homeostasis by modulating TcHRG expression independently of the source of available heme.
dc.description.filFil: Tevere, Evelyn. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Di Capua, Cecilia Beatriz. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Chasen, Nathan Michael. University of Georgia. Center for Tropical and Emerging Global Diseases (CTEGD). Department of Cellular Biology; United States.
dc.description.filFil: Etheridge, Ronald Drew. University of Georgia. Center for Tropical and Emerging Global Diseases (CTEGD). Department of Cellular Biology; United States.
dc.description.filFil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina.
dc.description.sponsorshipUK Research and Innovation via the Global Challenges Research Fund: grant agreement "A Global Network for Neglected Tropical Diseases" number MR/P027989/1
dc.description.sponsorshipAgencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Agencia I+D+i): PICT 2015-2437
dc.description.sponsorshipT32 Training in Tropical and Emerging Global Diseases: grant T32AI060546
dc.description.sponsorshipNational Institutes of Health (NIH): R01AI163140, R01GM144545
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
dc.format.extent1-23
dc.identifier.citationTevere, E., Di Capua, C. B., Chasen, N. M., Etheridge, R. D. and Cricco, J. A. (2024). Trypanosoma cruzi heme responsive gene (TcHRG) plays a central role in orchestrating heme uptake in epimastigotes. The FEBS Journal, 291(6), 1186-1198. https://doi.org/10.1111/febs.17030
dc.identifier.e-issn1742-4658
dc.identifier.issn1742-464X
dc.identifier.urihttps://hdl.handle.net/2133/28003
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofserieshttps://doi.org/10.1101/2023.04.05.535753
dc.relation.publisherversionhttps://doi.org/10.1111/febs.17030
dc.relation.publisherversionhttps://febs.onlinelibrary.wiley.com/doi/10.1111/febs.17030
dc.rightsopenAccess
dc.rights.holderTevere, Evelyn
dc.rights.holderDi Capua, Cecilia Beatriz
dc.rights.holderChasen, Nathan Michael
dc.rights.holderEtheridge, Ronald Drew
dc.rights.holderCricco, Julia Alejandra
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectTrypanosoma cruzi
dc.subjectChagas disease
dc.subjectHeme
dc.subjectHemoglobin
dc.subjectHeme transport
dc.subjectHRG
dc.subjectTcHRG
dc.titleTcHRG plays a central role in orchestrating heme uptake in Trypanosoma cruzi epimastigotes
dc.titleThe uptake of Hemoglobin-derived heme is mediated by TcHRG in 5 Trypanosoma cruzi epimastigotes
dc.titleTrypanosoma cruzi heme responsive gene (TcHRG) plays a central role in orchestrating heme uptake in epimastigotes
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionacceptedVersion

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