title: A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium.
abstract: Iron 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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Ksenija
authors.initials: K
authors.lastname: Slavic
authors.affiliation: Institute for Infection &Immunity, St. George's, University of London, London SW17 0RE, UK.
authors.forename: Sanjeev
authors.identifier: http://orcid.org/0000-0003-0066-0634
authors.initials: S
authors.lastname: Krishna
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Aparajita
authors.initials: A
authors.lastname: Lahree
authors.affiliation: Institute for Infection &Immunity, St. George's, University of London, London SW17 0RE, UK.|Sorbonne Universités, UPMC Univ Paris 6, CNRS, UMR 8227, Comparative Physiology of Erythrocytes, Station Biologique de Roscoff, CS 90074, 29688 Roscoff, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bouyer
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Hanson
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Iset
authors.initials: I
authors.lastname: Vera
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Jon K
authors.initials: JK
authors.lastname: Pittman
authors.affiliation: Institute for Infection &Immunity, St. George's, University of London, London SW17 0RE, UK.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Staines
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
mesh_terms: D000818:Animals; D002460:Cell Line; D005838:Genotype; D056945:Hep G2 Cells; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D007501:Iron