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

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.