Regulating the level of intracellular hydrogen peroxide: the role of peroxiredoxin IV.
Hydrogen peroxide (H2O2) can act as a signalling molecule affecting the cell cycle as well as contributing towards the oxidative stress response. The primary target of this molecule is oxidation-sensitive cysteine residues in proteins such as protein tyrosine phosphatases. The cell has robust mechanisms to remove H2O2 that need to be regulated for H2O2 to react with and modify protein thiols. In particular, the family of peroxiredoxins are capable of the rapid removal of even trace amounts of this molecule. It has been suggested that the inactivation of peroxiredoxins by hyperoxidation may allow H2O2 levels to increase in cells and thereby modify critical thiol groups in proteins. We have been studying how the H2O2 produced during disulfide formation in the ER (endoplasmic reticulum) is metabolized and have shown that ER-resident peroxiredoxin IV not only can remove H2O2, but also contributes to de novo disulfide formation. In the present article, we review recent data on the structure and function of this enzyme as well as its sensitivity to hyperoxidation.
*Institute of Molecular, Cellular and Systems Biology, College of Medical Veterinary and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, U.K.
Rachel E
RE
Martin
*Institute of Molecular, Cellular and Systems Biology, College of Medical Veterinary and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, U.K.
Zhenbo
Z
Cao
*Institute of Molecular, Cellular and Systems Biology, College of Medical Veterinary and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, U.K.
Neil J
NJ
Bulleid
D000818:Animals; D020134:Catalytic Domain; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000737:chemistry / Q000502:physiology*; D017433:Protein Structure, Secondary
D006861:Hydrogen Peroxide; D054464:Peroxiredoxins