Mitochondrial peroxiredoxin 3 is oxidized during Fas and TNF-α mediated apoptosis Free

3579

Stimulation of cellular death receptors is proposed to generate oxidants that contribute to the process of apoptosis. Oxidation of the peroxiredoxins and glyceraldehyde phosphate dehydrogenase are two sensitive cellular markers of increased H₂O₂ production and disruption of thiol homeostasis. We found that of these proteins only peroxiredoxin 3 was oxidised in Jurkat T lymphoma cells treated with anti-Fas antibody. Oxidation was detected at a similar time as activation of effector caspases. Interestingly, all of the peroxiredoxin 3 was captured as a disulfide-linked dimer rather than the overoxidised form, indicative of a disruption of the mitochondrial thioredoxin system rather than increased H₂O₂ production. Peroxiredoxin 3 oxidation was also observed in U937 cells stimulated with TNF-α, suggesting that this phenomenon may be a general feature of death receptor activated apoptosis. We propose that peroxiredoxin-3 oxidation is indicative of selective disruption of the mitochondrial redox environment, which leads to increased H₂O₂ production that contributes to apoptosis.