Mitochondrial respiratory chain involvement in peroxiredoxin 3 oxidation by phenethyl isothiocyanate and auranofin

作者：Brown Kristin K; Cox Andrew G; Hampton Mark B^*

来源：FEBS LETTERS, 2010, 584(6): 1257-1262.

DOI：10.1016/j.febslet.2010.02.042

• Hydrogen peroxide
• Redox signaling
• Oxidative stress
• Thioredoxin reductase
• Thioredoxin
• Mitochondria

Mitochondrial peroxiredoxin 3 (Prx 3) is rapidly oxidized in cells exposed to phenethyl isothiocyanate (PEITC) and auranofin (AFN), but the mechanism of oxidation is unclear. Using HL-60 cells deplete of mitochondrial DNA we show that peroxiredoxin 3 oxidation and cytotoxicity requires a functional respiratory chain. Thioredoxin reductase (TrxR) could be inhibited by up to 90% by auranofin without direct oxidation of peroxiredoxin 3. However, inhibition of thioredoxin reductase promoted peroxiredoxin 3 oxidation and cytotoxicity in combination with phenethyl isothiocyanate or antimycin A. We conclude that rapid peroxiredoxin 3 oxidation occurs as a consequence of increased oxidant production from the mitochondrial respiratory chain.

• 出版日期2010-3-19