CONICET | Buscador de Institutos y Recursos Humanos

To combat the deleterious effects that oxidation of the sulfur atom in methionine to sulfoxidemay bring, aerobic cells express repair pathways involving methionine sulfoxide reductases(MSRs) to reverse the above reaction. Here, we show that Trypanosoma brucei, the causativeagent of African trypanosomiasis, expresses two distinct trypanothione-dependent MSRs thatcan be distinguished from each other based on sequence, sub-cellular localisation andsubstrate preference. One enzyme found in the parasite?s cytosol, shows homology to theMSRA family of repair proteins and preferentially metabolises the S epimer of methioninesulfoxide. The second, which contains sequence motifs present in MSRBs, is restricted to themitochondrion and can only catalyse reduction of the R form of methionine sulfoxide. Theimportance of these proteins to the parasite was demonstrated using functional genomicbasedapproaches to produce cells with reduced or elevated expression levels of MSRA,which exhibited altered susceptibility to exogenous H2O2. These findings identify newreparative pathways that function to fix oxidatively damaged methionine within thismedically important parasite.