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

Abstract

Hydrogen peroxide emerged as major redox metabolite operative in redox sensing, signaling and redox regulation. Generation, transport and capture of H ₂O ₂ 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 H ₂O ₂ and on the role of H ₂O ₂ in redox signaling under physiological conditions (1–10 nM), denoted as oxidative eustress. Higher concentrations lead to adaptive stress responses via master switches such as Nrf2/Keap1 or NF-κB. Supraphysiological concentrations of H ₂O ₂ (>100 nM) lead to damage of biomolecules, denoted as oxidative distress. Three questions are addressed: How can H ₂O ₂ be assayed in the biological setting? What are the metabolic sources and sinks of H ₂O ₂? What is the role of H ₂O ₂ in redox signaling and oxidative stress?

Graphical abstract

Highlights

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  H ₂O ₂ is operative in redox sensing and redox signaling.

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  H ₂O ₂ reacts with metal centers and with sulfur/selenium compounds.

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  H ₂O ₂ links redox biology to phosphorylation/dephosphorylation.

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  Physiological (low-level, nM) steady-state of H ₂O ₂ is maintained in oxidative eustress.

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  Supraphysiological (pathological) level of H ₂O ₂ leads to oxidative distress.