CONICET | Buscador de Institutos y Recursos Humanos

Trypanosoma cruzi shows nutritional requirenments for different cofactors where heme is included. This organism lacks of any route for heme biosynthesis. However, it presents several heme-proteins included in essential metabolic pathways. T. cruzi must incorporate heme from the different hosts to supply for the heme-protein pool and also, as iron source. Recently several eucaryotic proteins were studied and asigned as heme transporters (or part of them) but, T. cruzi heme transporters have not being identified yet. In our laboratory we are interested in elucidate how heme is imported by T. cruzi, identifying and characterizing the proteins involved. We have used several fluorescent heme analogues (ZnPP, GaPP, ZnMP and SnMP) to study the heme transport in epimastigotes and amastigotes life stages of T. cruzi. The transport of heme analogues was followed by confocal microscopy and direct measurenment of fluorescence. We observed that all analogues impaired heme uptake in epimastigote competing for heme entrance but, not all were imported by the parasite. Only the incorporated analogues caused a negative effect on epimastigote proliferation, because they could not mimic heme functions. Besides, when cells infected with amastigotes were treated with fluorescent heme analogues, the fluorescent signal was selectively detected in amastigotes confirming that heme is transported in this intracellular life stage. Also, we identified a T. cruzi protein (named TcHR1) when expressed in yeast cells localized in plasma membrane and enhanced heme incorporation. As conclusion of our studies, we can postulate that T. cruzi imports heme during the replicative life stages. This parasite presents a selective protein transporter for heme uptake and the protein TcHR1 might play a relevant role in regulation and/or function of this transporter.