In malaria, Plasmodium parasites invade red blood cells (RBCs), a crucial step that enables their replication and contributes to disease progression. RBCs are an iron-rich environment, and Plasmodium parasites require iron for growth and replication, but how they obtain iron from RBCs has been unclear. Now, Loveridge and Sigala have uncovered a divalent metal transporter that is required for cellular iron metabolism in Plasmodium falciparum parasites.

Previous analyses indicated that P. falciparum encodes a protein homologue of human divalent metal transporter 1 (DMT1), which contributes to non-haem-associated cellular uptake of iron. Sequence, phylogenetic and molecular topology analyses by the authors suggest that P. falciparum DMT1 (PfDMT1) retains conserved molecular features that are important for metal transport. They went on to demonstrate that GFP-tagged PfDMT1 localizes to the parasite food vacuole membrane in an export-competent orientation. The parasite food vacuole is a specialized acidic organelle that has a key role in nutrient acquisition, and it functions in the digestion of haemoglobin obtained from the RBCs. Knockdown of PfDMT1 expression caused parasite death and these parasites had defects in iron-dependent cellular functions. Importantly, the parasites could be rescued by supplementation with exogenous iron. Overall, the study indicates that PfDMT1 is crucial for iron acquisition during RBC infection, and that it could serve as an antimalarial target.