A new model for heme homeostasis depends on modulation of HTE protein expression.

Heme is an essential cofactor for many biological processes in aerobic organisms, which can synthesize it through a conserved pathway. , the etiological agent of Chagas disease, as well as other trypanosomatids relevant to human health, are heme auxotrophs, meaning they must import it from their mammalian hosts or insect vectors. However, how these species import and regulate heme levels is not fully defined yet. It is known that the membrane protein HTE is involved in heme transport, although its specific role remains unclear. In the present work, we studied endogenous HTE in the different life cycle stages of the parasite to gain insight into its function in heme transport and homeostasis. We have confirmed that HTE is predominantly detected in replicative stages (epimastigote and amastigote), in which heme transport activity was previously validated. We also showed that in epimastigotes, HTE protein and mRNA levels decrease in response to increments in heme concentration, confirming it as a member of the heme response gene family. Finally, we demonstrated that epimastigotes can sense intracellular heme by an unknown mechanism and regulate heme transport to adapt to changing conditions. Based on these results, we propose a model in which senses intracellular heme and regulates heme transport activity by adjusting the expression of HTE. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding of a critical pathway for biology allowing the identification of novel and essential proteins.