Discussion

An Achilles’ heel of pathogenic trypanosomatid parasites is their absolute dependence on scavenging heme from their human hosts. Here, we unravel the mechanism used by Trypanosoma brucei and Leishmania to rescue heme from endocytosed hemoglobin. We show that parasite HRG transporters localize to the endolysosomal compartment, where hemoglobin is trafficked, and promote heme bioavailability after hemoglobin endocytosis. Using heme auxotrophic yeast mutants we demostrate that parasite HRG proteins enable yeast cells to exploit hemoglobin as a source of heme, increasing hemeprotein activity and rescuing the yeast growth defect. As these transporters are essential in T. brucei and Leishmania, their specific targeting could represent a novel method for controlling the neglected diseases caused by these parasites.