RT Journal Article
SR Electronic
T1 <em>Trypanosoma cruzi</em> senses intracellular heme levels and regulates heme homeostasis by modulating <em>Tc</em>HTE protein expression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.10.901934
DO 10.1101/2020.01.10.901934
A1 Lucas Pagura
A1 Evelyn Tevere
A1 Marcelo L. Merli
A1 Julia A. Cricco
YR 2020
UL http://biorxiv.org/content/early/2020/01/10/2020.01.10.901934.abstract
AB 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.TcHTET. cruzi Heme Transport Enhancer;rTcHTE.His-GFPrecombinant TcHTE;HRGHeme-response Gene;LHR1Leishmania heme response 1;TbHRGT. brucei heme-responsive gene;TMDtransmembrane domain;qRT-PCRquantitative real-time PCR;SnMPSn(IV) mesoporphyrin;ZnMPZn(II) mesoporphyrin;LITLiver Infusion Tryptose;DMEMDulbecco’s modified Eagle’s medium;FBSfetal bovine serum;DAPI4’,6-Diamidino-2-Phenylindole;GFPgreen fluorescent protein;MOImultiplicity of Infection;WTwild-type.