TcHRG plays a central role in orchestrating heme uptake inTrypanosoma cruziepimastigotes

Abstract

ABSTRACTTrypanosoma cruzi, a heme auxotrophic parasite, can control intracellular heme content by modulatingTcHRG expression when a free heme source is added to axenic culture. Herein, we explore the role ofTcHRG protein in regulating the uptake of heme derived from hemoglobin in epimastigotes. It was found that the parasite’s endogenousTcHRG (protein and mRNA) responds similarly to bound (hemoglobin) and free (hemin) heme. Additionally, the overexpression ofTcHRG leads to an increase in intracellular heme content. The localization ofTcHRG is also not affected in parasites supplemented with hemoglobin as the sole heme source. Endocytic null epimastigotes do not show a significant difference in growth profile, intracellular heme content andTcHRG protein accumulation compared to WT when feeding with hemoglobin or hemin as a source of heme. These results suggest that the uptake of hemoglobin-derived heme likely occurs through extracellular proteolysis of hemoglobinviathe flagellar pocket, and this process is governed byTcHRG. In sum,T. cruziepimastigotes controls heme homeostasis by modulatingTcHRG expression independently of the source of available heme.