Does Trypanosoma cruzi need heme? How is heme imported, distributed and used by it?

JULIA A CRICCO; LUCAS PAGURA; MARCELO L MERLI; BRENDA A. CIRULLI

Mar del Plata

Congreso; X Congreso de Protozoología y enfermedades parasitarias; 2014

Sociedad Argentina de Protozoología

SIMPOSIO Heme plays a fundamental role in many cellular processes. It is an essential cofactor for proteins involved in oxygen transport and storage, mitochondrial electron transport (Complex II?IV), drug and steroid metabolism (cytochromes), signal transduction (nitric oxide synthases, soluble guanylate cyclases), and transcription and regulation of antioxidant defense enzymes. Heme is also a regulatory molecule; its cytosolic to nuclear ratio and the absolute amount of its concentration affects gene transcription and translation; thus, the intracellular heme level must be tightly regulated. The heme biosynthetic pathway is highly conserved through evolution. Iron, porphyrins and heme are highly toxic to cells; therefore the level of free heme inside the cell is maintained very low. There is a tight control of its biosynthesis and degradation based on cellular requirements. Most of the eukaryotic organisms are able to synthesize heme, however, the medically relevant trypanosomes are completely (T. cruzi and T. brucei), or partially (Leishmania spp.), deficient in heme synthesis and they must scavenge this molecule from their hosts. Once heme is imported, it has to be distributed inside the cell and inserted into the target heme-proteins. But, the processes of heme transport and distribution in trypanosomatids remain unknown. Besides, these parasites present heme-proteins involved in essential metabolic pathways like biosynthesis of sterols and polyunsaturated fatty acids (PUFAs) carried out in the endoplasmic reticulum (ER) and respiratory complexes in the mitochondrion. The understanding of how they import, distribute, utilize heme, and assemble heme-proteins can help elucidate the essential metabolic pathway in these trypanosomatids. We are interested in elucidating how T. cruzi imports, distributes and uses heme. Our results showed that this parasite takes heme from the environment (host), at least during the replicative life stages, and distributes heme inside cell. The blockage of heme transport or mitochondrial heme modification negatively affects cell proliferation.