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A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium

dc.contributor.authorSlavic, Ksenija
dc.contributor.authorKrishna, Sanjeev
dc.contributor.authorLahree, Aparajita
dc.contributor.authorBouyer, Guillaume
dc.contributor.authorHanson, Kirsten K.
dc.contributor.authorVera, Iset
dc.contributor.authorPittman, Jon K.
dc.contributor.authorStaines, Henry M.
dc.contributor.authorMota, Maria M.
dc.date.accessioned2022-03-07T15:37:08Z
dc.date.available2022-03-07T15:37:08Z
dc.date.issued2016
dc.description© Copyright © 2016, The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/pt_PT
dc.description.abstractIron is an essential micronutrient but is also highly toxic. In yeast and plant cells, a key detoxifying mechanism involves iron sequestration into intracellular storage compartments, mediated by members of the vacuolar iron-transporter (VIT) family of proteins. Here we study the VIT homologue from the malaria parasites Plasmodium falciparum (PfVIT) and Plasmodium berghei (PbVIT). PfVIT-mediated iron transport in a yeast heterologous expression system is saturable (Km ∼ 14.7 μM), and selective for Fe(2+) over other divalent cations. PbVIT-deficient P. berghei lines (Pbvit(-)) show a reduction in parasite load in both liver and blood stages of infection in mice. Moreover, Pbvit(-) parasites have higher levels of labile iron in blood stages and are more sensitive to increased iron levels in liver stages, when compared with wild-type parasites. Our data are consistent with Plasmodium VITs playing a major role in iron detoxification and, thus, normal development of malaria parasites in their mammalian host.pt_PT
dc.description.sponsorshipThis work was supported by grants from the European Research Council ERC-2012-StG_311502 to M.M.M., Fundação para a Ciência e Tecnologia EXPL/BIM-MET/0753/2013 and The European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n°. 304948—NANOMAL to S.K. and H.M.S. K.S. was supported by an EMBO long-term fellowship (EMBO ALTF 1584-2011).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Commun. 2016 Jan 20;7:10403pt_PT
dc.identifier.doi10.1038/ncomms10403pt_PT
dc.identifier.eissn2041-1723
dc.identifier.urihttp://hdl.handle.net/10451/51630
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationERC-2012-StG_311502pt_PT
dc.relationDevelopment of a handheld antimalarial drug resistance diagnostic device using nanowire technology
dc.relation.publisherversionhttps://www.nature.com/ncomms/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleA vacuolar iron-transporter homologue acts as a detoxifier in Plasmodiumpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDevelopment of a handheld antimalarial drug resistance diagnostic device using nanowire technology
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FBIM-MET%2F0753%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/304948/EU
oaire.citation.issue1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume7pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamFP7
person.familyNameSlavic
person.familyNameLahree
person.familyNameHanson
person.familyNameVera
person.familyNameMota
person.givenNameKsenija
person.givenNameAparajita
person.givenNameKirsten
person.givenNameIset
person.givenNameMaria Manuel
person.identifier.ciencia-id3416-653D-20B9
person.identifier.ciencia-id4217-0969-297E
person.identifier.orcid0000-0002-3620-553X
person.identifier.orcid0000-0002-2341-7269
person.identifier.orcid0000-0002-0154-0979
person.identifier.orcid0000-0003-4835-9437
person.identifier.orcid0000-0002-2858-1041
person.identifier.scopus-author-id28167771800
person.identifier.scopus-author-id55802537000
person.identifier.scopus-author-id16308336900
person.identifier.scopus-author-id7102709816
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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