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

Abstract

ABSTRACTHeme is an essential cofactor for many biological processes in aerobic organisms. Unlike most organisms, which can synthesize it de novo through a conserved pathway, the etiological agent of Chagas disease, Trypanosoma cruzi, as well as other trypanosomatids relevant for human health, are heme auxotrophs; thereby they must import it from the hosts. TcHTE protein is involved in T. cruzi heme transport, although its specific role remains elusive. In the present work we studied endogenous TcHTE 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 TcHTE is predominantly detected in replicative stages (epimastigote and amastigote). We have also demonstrated that T. cruzi 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 T. cruzi senses intracellular heme and regulates heme transport activity adjusting the expression of TcHTE. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding of T. cruzi biology as well as other trypanosomatids, pointing out this pathway as a novel drug target for therapeutics.