The trypanothione system.

Trypanosomes and Leishmania, the causative agents of severe tropical diseases, employ 2-Cys-peroxiredoxins together with cysteine-homologues of glutathione peroxidases and ascorbate-dependent peroxidases for the detoxification of hydroperoxides. All three types of peroxidases gain their reducing equivalents from the parasite-specific dithiol trypanothione [bis(glutathionyl)spermidine]. Based on their primary structure and cellular localization, the trypanosomatid 2-Cys-peroxiredoxins are subdivided into two families that occur in the mitochondrion and cytosol of the parasites. In Trypanosoma brucei, the cytosolic 2-Cys-peroxiredoxin, as well as the glutathione peroxidase-type enzyme, is essential for cell viability. Despite overlapping substrate specificities and subcellular localizations, the two types of peroxidases can obviously not substitute for each other which suggests distinct cell-physiological roles.