Quantitative biology of hydrogen peroxide signaling

Abstract

Hydrogen peroxide (H₂O₂) controls signaling pathways in cells by oxidative modulation of the activity of redox sensitive proteins denominated redox switches. Here, quantitative biology concepts are applied to review how H₂O₂ fulfills a key role in information transmission. Equations described lay the foundation of H₂O₂ signaling, give new insights on H₂O₂ signaling mechanisms, and help to learn new information from common redox signaling experiments. A key characteristic of H₂O₂ signaling is that the ratio between reduction and oxidation of redox switches determines the range of H₂O₂ concentrations to which they respond. Thus, a redox switch with low H₂O₂-dependent oxidability and slow reduction rate responds to the same range of H₂O₂ concentrations as a redox switch with high H₂O₂-dependent oxidability, but that is rapidly reduced. Yet, in the first case the response time is slow while in the second case is rapid. H₂O₂ sensing and transmission of information can be done directly or by complex mechanisms in which oxidation is relayed between proteins before oxidizing the final regulatory redox target. In spite of being a very simple molecule, H₂O₂ has a key role in cellular signaling, with the reliability of the information transmitted depending on the inherent chemical reactivity of redox switches, on the presence of localized H₂O₂ pools, and on the molecular recognition between redox switches and their partners.

Keywords: Dynamic range; Information transmission; Kinetics; Redox switches; Response time; Steady-state.