A reaction-diffusion model of cytosolic hydrogen peroxide.

Abstract As a signaling molecule in mammalian cells, hydrogen peroxide (H 2 O 2 ) determines the thiol/disulfide oxidation state of several key proteins in the cytosol. Localization is a key concept in redox signaling; the concentrations of signaling molecules within the cell are expected to vary in time and in space in manner that is essential for function. However, as a simplification, all theoretical studies of intracellular hydrogen peroxide and many experimental studies to date have treated the cytosol as a well-mixed compartment. In this work, we incorporate our previously reported reduced kinetic model of the network of reactions that metabolize hydrogen peroxide in the cytosol into a model that explicitly treats diffusion along with reaction. We modeled a bolus addition experiment, solved the model analytically, and used the resulting equations to quantify the spatiotemporal variations in intracellular H 2 O 2 that result from this kind of perturbation to the extracellular H 2 O 2 concentration. We predict that micromolar bolus additions of H 2 O 2 to suspensions of HeLa cells (0.8×10 9  cells/l) result in increases in the intracellular concentration that are localized near the membrane. These findings challenge the assumption that intracellular concentrations of H 2 O 2 are increased uniformly throughout the cell during bolus addition experiments and provide a theoretical basis for differing phenotypic responses of cells to intracellular versus extracellular perturbations to H 2 O 2 levels.