The Role of Hydrogen Peroxide and Peroxiredoxins throughout the Cell Cycle

Hydrogen peroxide (H₂O₂) is an oxidizing agent that induces cellular damage at inappropriate concentrations and gives rise to an arrest during cell cycle progression, causing cell death. Recent evidence indicates that H₂O₂ also acts as a promoter for cell cycle progression by oxidizing specific thiol proteins. The intracellular concentration of H₂O₂ is regulated tightly, enabling its use as a cellular signaling molecule while minimizing its potential to cause cellular damage. Peroxiredoxins (Prxs) have peroxidase activity toward H₂O₂, organic hydroperoxides, and peroxynitrite for protecting cells from oxidative stress. They are suggested to work as signaling mediators, allowing the local accumulation of H₂O₂ by inactivating their peroxidase activity uniquely compared with other antioxidant proteins such as catalase and glutathione peroxidase. Given that Prxs are highly sensitive to oxidation by H₂O₂, they act as sensors and transducers of H₂O₂ signaling via transferring their oxidation state to effector proteins. The concentrations of intracellular H₂O₂ increase as the cell cycle progresses from G₁ to mitosis. Here, we summarize the roles of Prxs with regard to the regulation of cell cycle-dependent kinase activity and anaphase-promoting complex/cyclosome in terms of changes in H₂O₂ levels. Protection of the cell from unwanted progression of the cell cycle is suggested to be a role of Prx. We discuss the possible roles of Prxs to control H₂O₂ levels.