New Insights on Heme Uptake in Leishmania spp

The protozoan parasite Leishmania, responsible for leishmaniasis, is one of the few aerobic organisms that cannot synthesize the essential molecule heme. Therefore, it has developed specialized pathways to scavenge it from its host. In recent years, some proteins involved in the import of heme, such...

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Autores: Cabello-Donayre, María, Orrego, Lina M., Herráez, Elisa, García-Hernández, Raquel, Pérez-Victoria, José M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/280386
Acceso en línea:http://hdl.handle.net/10261/280386
Access Level:acceso abierto
Palabra clave:Heme
Porphyrin trafficking
Leishmania
Protozoan parasites
Neglected diseases
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spelling New Insights on Heme Uptake in Leishmania sppCabello-Donayre, MaríaOrrego, Lina M.Herráez, ElisaGarcía-Hernández, RaquelPérez-Victoria, José M.HemePorphyrin traffickingLeishmaniaProtozoan parasitesNeglected diseasesThe protozoan parasite Leishmania, responsible for leishmaniasis, is one of the few aerobic organisms that cannot synthesize the essential molecule heme. Therefore, it has developed specialized pathways to scavenge it from its host. In recent years, some proteins involved in the import of heme, such as LHR1 and LFLVCRB, have been identified, but relevant aspects regarding the process remain unknown. Here, we characterized the kinetics of the uptake of the heme analogue Zn(II) Mesoporphyrin IX (ZnMP) in Leishmania major promastigotes as a model of a parasite causing cutaneous leishmaniasis with special focus on the force that drives the process. We found that ZnMP uptake is an active, inducible, and pH-dependent process that does not require a plasma membrane proton gradient but requires the presence of the monovalent cations Na+ and/or K+. In addition, we demonstrated that this parasite can efflux this porphyrin against a concentration gradient. We also found that ZnMP uptake differs among different dermotropic or viscerotropic Leishmania species and does not correlate with LHR1 or LFLVCRB expression levels. Finally, we showed that these transporters have only partially overlapping functions. Altogether, these findings contribute to a deeper understanding of an important process in the biology of this parasite.This research was funded by the Spanish Ministerio de Ciencia e Innovación (SAF2016-80228-R and PID2019-106724RB-I00 to JMPV), Junta de Andalucía (P12-BIO-1786 and P18-RT-3052 to JMPV), “Fundación Samuel Solórzano Barruso” (FS/7-2016 to EH), and FEDER funds from the EU to JMPV.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Junta de AndalucíaFundación Memoria de D. Samuel Solorzano BarrusoEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/280386reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106724RB-I00info:eu-repo/grantAgreement/MINECO//SAF2016-80228-Rhttps://doi.org/10.3390/ijms231810501Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2803862026-05-22T06:33:51Z
dc.title.none.fl_str_mv New Insights on Heme Uptake in Leishmania spp
title New Insights on Heme Uptake in Leishmania spp
spellingShingle New Insights on Heme Uptake in Leishmania spp
Cabello-Donayre, María
Heme
Porphyrin trafficking
Leishmania
Protozoan parasites
Neglected diseases
title_short New Insights on Heme Uptake in Leishmania spp
title_full New Insights on Heme Uptake in Leishmania spp
title_fullStr New Insights on Heme Uptake in Leishmania spp
title_full_unstemmed New Insights on Heme Uptake in Leishmania spp
title_sort New Insights on Heme Uptake in Leishmania spp
dc.creator.none.fl_str_mv Cabello-Donayre, María
Orrego, Lina M.
Herráez, Elisa
García-Hernández, Raquel
Pérez-Victoria, José M.
author Cabello-Donayre, María
author_facet Cabello-Donayre, María
Orrego, Lina M.
Herráez, Elisa
García-Hernández, Raquel
Pérez-Victoria, José M.
author_role author
author2 Orrego, Lina M.
Herráez, Elisa
García-Hernández, Raquel
Pérez-Victoria, José M.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Junta de Andalucía
Fundación Memoria de D. Samuel Solorzano Barruso
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Heme
Porphyrin trafficking
Leishmania
Protozoan parasites
Neglected diseases
topic Heme
Porphyrin trafficking
Leishmania
Protozoan parasites
Neglected diseases
description The protozoan parasite Leishmania, responsible for leishmaniasis, is one of the few aerobic organisms that cannot synthesize the essential molecule heme. Therefore, it has developed specialized pathways to scavenge it from its host. In recent years, some proteins involved in the import of heme, such as LHR1 and LFLVCRB, have been identified, but relevant aspects regarding the process remain unknown. Here, we characterized the kinetics of the uptake of the heme analogue Zn(II) Mesoporphyrin IX (ZnMP) in Leishmania major promastigotes as a model of a parasite causing cutaneous leishmaniasis with special focus on the force that drives the process. We found that ZnMP uptake is an active, inducible, and pH-dependent process that does not require a plasma membrane proton gradient but requires the presence of the monovalent cations Na+ and/or K+. In addition, we demonstrated that this parasite can efflux this porphyrin against a concentration gradient. We also found that ZnMP uptake differs among different dermotropic or viscerotropic Leishmania species and does not correlate with LHR1 or LFLVCRB expression levels. Finally, we showed that these transporters have only partially overlapping functions. Altogether, these findings contribute to a deeper understanding of an important process in the biology of this parasite.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/280386
url http://hdl.handle.net/10261/280386
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106724RB-I00
info:eu-repo/grantAgreement/MINECO//SAF2016-80228-R
https://doi.org/10.3390/ijms231810501
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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