TcHTE modulates heme transport in Trypanosoma cruzi

EVELYN TEVERE; JULIA A. CRICCO; LUCAS PAGURA; SEBASTIÁN BRAUCHI; ELLA MATAMALA

Ciudad Autónoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017

Sociedades Argentinas de Biociencias. SAP, SAB. SAIB, etc

Trypanosoma cruzi, the parasite responsible of Chagas disease, presents auxotrophy for heme. It contains several heme-proteins involved in essential metabolic pathway such us mitochondrial respiratory complexes, unsaturated fatty acid and ergosterol biosynthesis. It must take heme from the different hosts to supply this requirement, being heme transport and distribution essential for the parasite survival. We are interested in elucidating how heme is acquired and used by T. cruzi and to accomplish this, different strategies are utilized.T. cruzi presents a dedicated system to transport heme that can discriminate between structurally related compounds, as it was observed by confocal microscopy and fluorescence measurements using fluorescent heme analogs (HAs). Also, we have shown that heme (HAs) was selectively taken by the parasite replicative stages where the protein we named TcHTE (T. cruzi Heme Transport Enhancer protein) plays an essential role. TcHTE belongs to HRG family proteins described in C. elegans (Heme Response Genes) and also conserved in trypanosomatids. These proteins show four putative transmembrane domains and no homology to other reported transporters. Our results demonstrate that TcHTE protein level changes according to heme availability, being almost no detected when epimastigotes were maintained in a media with adequate heme source (hemin). Surprisingly, the recombinant TcHTE-GFP was clearly located in the flagellar pocket region of the parasite, where the metabolites transport seems to proceed in trypanosomatids, with its C-terminal domain facing the cytoplasm of the cell. The expression of the rTcHTE-GFP in HECK293 cells allowed the analysis of oligomers formation by TIRF microscopy, where our preliminary results showed that TcHTE could form trimers.In summary, our results indicate that TcHTE plays an essential role modulating the heme transport activity in T. cruzi, presumably being part of a sophisticated complex transporter system.