Role of Metabolic H2O2 Generation: Redox Signalling and Oxidative Stress. [Bioenergetics]

February 10th, 2014 by Sies, H.

Hydrogen peroxide, the non-radical two-electron reduction product of oxygen, is a normal aerobic metabolite occurring at about 10 nM intracellular concentration. In liver, it is produced at 50 nmol per min per gram of tissue, which is about 2 % of total oxygen uptake at steady-state. Metabolically generated H2O2 emerged from recent research as central hub in redox signalling and oxidative stress. Upon generation by major sources, the NADPH oxidases or Complex III of the mitochondrial respiratory chain, H2O2 is under sophisticated fine-control of peroxiredoxins and glutathione peroxidases with their back-up systems as well as by catalase. Of note, H2O2 is second messenger in insulin signalling and in several growth factor-induced signalling cascades. H2O2 transport across membranes is facilitated by aquaporins, denoted as peroxiporins. Specialized protein cysteines operate as redox switches using H2O2 as thiol oxidant, making this reactive oxygen species essential for poising the setpoint of the redox proteome. Major processes including proliferation, differentiation, tissue repair, inflammation, circadian rhythm and aging use this low-molecular-weight oxygen metabolite as signalling compound.