Trypanosoma cruzi senses intracellular heme levels and regulates heme homeostasis by modulating Tc HTE protein expression

Heme is an essential cofactor for many biological processes in aerobic organisms. Unlike most organisms, which can synthesize it through a conserved pathway, the etiological agent of Chagas disease, , as well as other trypanosomatids relevant for human health, are heme auxotrophs; thereby they must import it from the hosts. HTE protein is involved in heme transport, although its specific role remains elusive. In the present work we studied endogenous HTE in the different life cycle stages of the parasite in order to gain insight in its function in heme transport and homeostasis. We have confirmed that HTE is predominantly detected in replicative stages (epimastigote and amastigote). We have also demonstrated that epimastigotes can sense intracellular heme content by an unknown mechanism and regulates 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 adjusting the expression of HTE. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding of biology as well as other trypanosomatids, pointing out this pathway as a novel drug target for therapeutics.