CONICET | Buscador de Institutos y Recursos Humanos

Heme transport, trafficking and uses by Trypanosoma cruzi Trypanosoma cruzi is the etiological agent of the Chagas disease. This parasite presents a complex life cycle, altering between a mammalian hosts and an insect vector. It needs to adapt to different environments and energy sources. T. cruzi, like other trypanosomatids, has requirements for several essential cofactors included heme. Previous biochemical studies, have demonstrated the absence of a complete heme biosynthetic pathway that lately was corroborated by the sequencing of the parasite genome revealing the lack of eight enzymes of the classical glycine pathway.This parasite has to import heme from the environment, distribute and inserted it into different heme-proteins, some of them involved in essential metabolic routes. We wanted to elucidate how heme is imported and distributed among the cell by T. cruzi, specially focused in its transport to mitochondria. As a first approach to understand heme uptake processes, we designed and optimized conditions to study the biochemical properties of the transport using a fluorescent heme analog in epimastigotes of T. cruzi. We observed that heme import is mediated by a membrane active transporter, depending of ATP and sensitive to cation gradients. The heme uptake was inhibited by the presence of ABC transporters inhibitors.Although the energetic metabolism of T. cruzi is not completely elucidated, different studies have demonstrated that this parasite depend on the mitochondrial respiratory chain activity during several stages of its life cycle. In this way, heme has to be transported to mitochondria and inserted into the respiratory complexes. We will present studies on T. cruzis heme A biosynthesis, the essential cofactor of cytochrome c oxidase enzyme. The enzymes involved in the process were identified and their function studied using yeast Saccharomyces cereviseae as heterologuos expression system.