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 Fe2+ 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.

Two viruses, MCV1 and MCV2, which infect Marinitoga bacteria isolated from deep‐sea hydrothermal vents: functional and genomic analysis

“…For Thermococcales it was demonstrated that MVs could be a defense system for cells by preventing toxic accumulation of sulfur (Gorlas et al, 2015). Similarly, several studies on eukaryotes and bacteria have shown that membrane vesicles can play a role in detoxification (Sterling et al, 2007;Jagannadham and Chattopadhyay, 2015;Slavic et al, 2016). The phenomenon was first observed in eukaryotic marine organisms such as mollusks and crustaceans, which accumulate cadmium and where excretion of cadmium is performed by MVs as a detoxifying mechanism (Sterling et al, 2007).…”

Wheat Vacuolar Iron Transporter TaVIT2 Transports Fe and Mn and Is Effective for Biofortification

“…However, currently, there is no crystal structure of any of the VIT family members and no other good structural homology models. Recently, a first glimpse into the transport mechanism was provided, showing that P. falciparum VIT1 is an H + antiporter with strong selectivity for Fe 2+ (Slavic et al, 2016;Labarbuta et al, 2017).…”

“…Expression of Arabidopsis VIT1 also increases the manganese content of yeast cells (Kim et al, 2006), and it has a supporting role in manganese transport in Arabidopsis embryos (Eroglu et al, 2017). The VITs form a unique transporter family, found in plants, fungi, and protists such as the malarial parasite Plasmodium falciparum, but they are absent from metazoans (Slavic et al, 2016). VITs in plants share a high degree of sequence similarity and the capacity to transport iron, but their biological functions may differ.…”

Transmembrane solute transport in the apicomplexan parasite Plasmodium

“…The second is an orthologue of the vacuolar iron transporter, VIT, family, members of which are proposed to transport Fe 2+ into acidic vacuoles. Using the yeast heterologous expression system, P. falciparum VIT was shown to transport Fe 2+ with low micromolar affinity, in the first functional characterisation of a member of the VIT family [45]. It was later demonstrated to exchange Fe 2+ for protons [46].…”

“…As with ZIPCO, P. berghei VIT was found not to be essential. However, it is important for both blood and liver stages of parasite growth, providing a tolerance mechanism against excess iron, and may localise to the parasite's endoplasmic reticulum [45]. The third and most recently characterised iron transporter is PfCRT.…”