Mitochondrial Antioxidants and the Maintenance of Cellular Hydrogen Peroxide Levels

Figure 3

Hydrogen peroxide is a secondary messenger that transmits information in the cytosol using two different mechanisms: the floodgate and redox relay models. The floodgate model involves the activation of cell surface receptors by a physiological stimulus. This induces cell signaling cascades that also activate NADPH oxidase (NOX), activating the production of H₂O₂. The hydrogen peroxide yielded from NOX activation, results in the oxidative deactivation of peroxiredoxin-1 (PRX1). Hydrogen peroxide subsequently accumulates, inducing cell signaling pathways or reinforcing others through the deactivation of phosphatases. Reactivation of PRX1 requires sulfiredoxin (SRX). The redox relay model uses a series of thiol disulfide exchange reactions to activate or deactivate a target protein. Hydrogen peroxide generated by a physiological stimulus is first quenched by PRX2 forming a sulfenic acid on the peroxidatic catalytic cysteine. The sulfenic acid is resolved by a second cysteine forming a disulfide bridge. PRX2 is then reduced by STAT3 by a thiol disulfide exchange reaction.