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Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi

Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi

Wilkinson, Shane R., Temperton, Nigel J. ORCID: 0000-0002-7978-3815, Mondragon, Angeles and Kelly, John M. (2000) Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi. The Journal of Biological Chemistry, 275 (11). pp. 8220-8225. ISSN 0021-9258 (Print), 1083-351X (Online) (doi:https://doi.org/10.1074/jbc.275.11.8220)

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Abstract

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 in T. 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. cruzi cytoplasmic peroxiredoxin and T. cruzi mitochondrial peroxiredoxin may be exploitable in terms of drug development.

Item Type: Article
Additional Information: [1] This article is free access [2] The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AJ006226 (TcMPX) and AJ012101 (TcCPX).
Uncontrolled Keywords: proteins, T. cruzi, peroxide-mediated damage, enzyme activity, cytoplasmic peroxiredoxin, mitochondrial peroxiredoxin
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine
Faculty / School / Research Centre / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Medway School of Pharmacy
Related URLs:
Last Modified: 14 Jul 2015 15:59
URI: http://gala.gre.ac.uk/id/eprint/8569

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