Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress.

Hydrogen peroxide emerged as major redox metabolite operative in redox sensing, signaling and redox regulation. Generation, transport and capture of HO in biological settings as well as their biological consequences can now be addressed. The present overview focuses on recent progress on metabolic sources and sinks of HO and on the role of HO in redox signaling under physiological conditions (1-10nM), denoted as oxidative eustress. Higher concentrations lead to adaptive stress responses via master switches such as Nrf2/Keap1 or NF-κB. Supraphysiological concentrations of HO (>100nM) lead to damage of biomolecules, denoted as oxidative distress. Three questions are addressed: How can HO be assayed in the biological setting? What are the metabolic sources and sinks of HO? What is the role of HO in redox signaling and oxidative stress?