Distinct Mitochondrial and Cytosolic Enzymes Mediate Trypanothione-dependent Peroxide Metabolism in Trypanosoma cruzi

The American trypanosome Trypanosoma cruzi is exposed to toxic oxygen metabolites that are generated by drug metabolism and immune responses in addition to those produced by endogenous processes. However, much remains to be resolved about the parasite oxidative defense system, including the mechanis...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-03, Vol.275 (11), p.8220-8225
Main Authors: Wilkinson, Shane R., Temperton, Nigel J., Mondragon, Angeles, Kelly, John M.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell Compartmentation
Cytosol - enzymology
Dimerization
Drug Resistance
Genes, Protozoan
Glutathione - analogs & derivatives
Glutathione - metabolism
Hydrogen Peroxide - metabolism
Hydrogen Peroxide - toxicity
Mitochondria - enzymology
Molecular Sequence Data
Peroxidases - genetics
Peroxidases - isolation & purification
Peroxidases - metabolism
peroxide
Protein Structure, Quaternary
Sequence Homology, Amino Acid
Spermidine - analogs & derivatives
Spermidine - metabolism
Trypanosoma cruzi
Trypanosoma cruzi - enzymology
trypanothione
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Summary:The American trypanosome Trypanosoma cruzi is exposed to toxic oxygen metabolites that are generated by drug metabolism and immune responses in addition to those produced by endogenous processes. However, much remains to be resolved about the parasite oxidative defense system, including the mechanism(s) of peroxide reduction. Here we show that reduction of peroxides inT. cruzi is catalyzed by two distinct trypanothione-dependent enzymes. These were localized to the cytosol and mitochondrion. Both are members of the peroxiredoxin family of antioxidant proteins and are characterized by the presence of two conserved domains containing redox active cysteines. The role of these proteins in protecting T. cruzi from peroxide-mediated damage was demonstrated following overexpression of enzyme activity. The parasite-specific features of T. cruzicytoplasmic peroxiredoxin and T. cruzi mitochondrial peroxiredoxin may be exploitable in terms of drug development.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.275.11.8220