Figure 1

Re-activation of PRDXs. (1) PRDXs scavenge H₂O₂ and become oxidized and inactive (2). This inactivation is reversed by the thioredoxin (TRX)-TRX reductase (TRD) system that uses NADPH as reducing equivalents (3). (4) Further thiol oxidation of PRDXs by higher levels of H₂O₂ (hyperoxidation) radically inactivates the enzyme allowing H₂O₂ levels to increase in the cell and to trigger the H₂O₂-dependent signaling. This inactivation must be transient to avoid toxic effects by high levels of H₂O₂; thus, after transmission of the signal, SRX/sestrins re-activate PRDXs using ATP (P = phosphate group) (5). (6) Finally, donors of SH groups such as GSH or TRX, reduce PRDX.