A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium
Résumé
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 (KmB14.7 mM), and selective for Fe2þ 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.
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Origine : Fichiers éditeurs autorisés sur une archive ouverte