Mitochondrial peroxiredoxin 3 is more resilient to hyperoxidation than cytoplasmic peroxiredoxins.
The Prxs (peroxiredoxins) are a family of cysteine-dependent peroxidases that decompose hydrogen peroxide. Prxs become hyperoxidized when a sulfenic acid formed during the catalytic cycle reacts with hydrogen peroxide. In the present study, Western blot methodology was developed to quantify hyperoxidation of individual 2-Cys Prxs in cells. It revealed that Prx 1 and 2 were hyperoxidized at lower doses of hydrogen peroxide than would be predicted from in vitro data, suggesting intracellular factors that promote hyperoxidation. In contrast, mitochondrial Prx 3 was considerably more resistant to hyperoxidation. The concentration of Prx 3 was estimated at 125 microM in the mitochondrial matrix of Jurkat T-lymphoma cells. Although the local cellular environment could influence susceptibility, purified Prx 3 was also more resistant to hyperoxidation, suggesting that despite having C-terminal motifs similar to sensitive eukaryote Prxs, other structural features must contribute to the innate resilience of Prx 3 to hyperoxidation.
Cox
Andrew G
AG
Free Radical Research Group and National Research Centre for Growth and Development, Department of Pathology, University of Otago, Christchurch, New Zealand.
Pearson
Andree G
AG
Pullar
Juliet M
JM
Jönsson
Thomas J
TJ
Lowther
W Todd
WT
Winterbourn
Christine C
CC
Hampton
Mark B
MB
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism*; D011487:Protein Conformation; D021381:Protein Transport
D054464:Peroxiredoxins