Pathways of iron acquisition and utilization in Leishmania

•Iron and heme acquisition are essential for Leishmania virulence.•Leishmania express LFR1, a transmembrane ferric reductase that converts Fe3+ in Fe2+.•The Leishmania ferrous iron transporter express LIT1 translocates Fe2+ to the cytosol.•The Leishmania heme transporter LHR1 translocates heme into the parasite's cytosol.•LFR1, LIT1 and LHR1 expression is upregulated under low iron availability.

Iron is essential for many metabolic pathways, but is toxic in excess. Recent identification of the ferric iron reductase LFR1, the ferrous iron transporter LIT1, and the heme transporter LHR1 greatly advanced our understanding of how Leishmania parasites acquire iron and regulate its uptake. LFR1 and LIT1 have close orthologs in plants, and are required for Leishmania virulence. Consistent with the lack of heme biosynthesis in trypanosomatids, LHR1 and LABCG5, a protein involved in heme salvage from hemoglobin, seem essential for Leishmania survival. LFR1, LIT1 and LHR1 are upregulated under low iron availability, in agreement with the need to prevent excessive iron uptake. Future studies should clarify how Leishmania interacts with the iron homeostasis machinery of its host cell, the macrophage.