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

By Lucas Pagura, Evelyn Tevere, Marcelo L. Merli, Julia A. Cricco

Posted 10 Jan 2020
bioRxiv DOI: 10.1101/2020.01.10.901934

Heme is an essential cofactor for many biological processes in aerobic organisms. Most of them can synthesize it de novo via a conserved pathway. Trypanosoma cruzi , the etiological agent of Chagas disease, 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 study endogenous and recombinant TcHTE in the different life cycle stages of the parasite, in order to approach to its function in heme transport and heme homeostasis. We have confirmed that TcHTE belongs to the HRG protein family, it is predominantly detected in replicative stages (epimastigote and amastigote) and localized mainly in the flagellar pocket of the parasite. We have also demonstrated that T. cruzi epimastigotes can sense intracellular heme content by an unknown mechanism and are able to modulate the expression of TcHTE in order to regulate heme transport. Based on these results, we propose a model in which T. cruzi regulates heme transport activity adjusting the amount of TcHTE present in the cell. This work is, to our knowledge, the first study of an endogenous trypanosomatid HRG protein. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding of the biology of T. cruzi , a parasite relevant for human health.

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