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 H₂O₂ 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 H₂O₂ and on the role of H₂O₂ 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 H₂O₂ (>100nM) lead to damage of biomolecules, denoted as oxidative distress. Three questions are addressed: How can H₂O₂ be assayed in the biological setting? What are the metabolic sources and sinks of H₂O₂? What is the role of H₂O₂ in redox signaling and oxidative stress?