Redox Biology And Oxidative Stress

A long-standing focus of my basic research is the quantitative biology of reactive oxygen species, particularly hydrogen peroxide, at physiologically relevant concentrations.

The development of an ultrasensitive non-enzymatic chemiluminescence assay enabled real-time analysis of hydrogen peroxide metabolism in enzymes, erythrocytes, organelles and intact cells. This work established catalase as the predominant peroxide-removing enzyme in human erythrocytes and enabled direct measurement of peroxide release from intact peroxisomes.

Building on this assay, we developed the GOX/CAT system to independently control oxygen and steady-state hydrogen peroxide concentrations in cultured cells. Using this system, we showed that HIF-1α responds primarily to the rapid decline in oxygen rather than to hypoxia per se. We further demonstrated that sustained submicromolar hydrogen peroxide induces the iron-regulatory hormone hepcidin through STAT3 signalling, establishing a direct mechanistic link between redox signalling and systemic iron metabolism. These approaches were also used to study cellular responses to sustained low-dose peroxide and H₂O₂-mediated autophagy during ethanol metabolism.

Selected publications

Fast and sensitive chemiluminescence determination of H2O2 concentration in stimulated human neutrophils. Mueller S, Arnhold J. J Biolumin Chemilumin. 1995;10(4):229–237.
Direct evidence for catalase as the predominant H2O2-removing enzyme in human erythrocytes. Mueller S, Riedel HD, Stremmel W. Blood. 1997;90(12):4973–4978.
Sensitive and real-time determination of H2O2 release from intact peroxisomes. Mueller S et al. Biochem J. 2002;363(Pt 3):483–491.
Hypoxia-inducible factor 1 alpha under rapid enzymatic hypoxia: cells sense decrements of oxygen but not hypoxia per se. Millonig G et al. Free Radic Biol Med. 2009;46(2):182–191.
The GOX/CAT system: A novel enzymatic method to independently control hydrogen peroxide and hypoxia in cell culture. Mueller S, Millonig G, Waite GN. Adv Med Sci. 2009;54:121–135.
Sustained submicromolar H2O2 levels induce hepcidin via signal transducer and activator of transcription 3 (STAT3). Millonig G et al. J Biol Chem. 2012;287(44):37472–37482.
Exposing cells to H2O2: a quantitative comparison between continuous low-dose and one-time high-dose treatments. Sobotta MC et al. Free Radic Biol Med. 2013;60:325–335.
H2O2-mediated autophagy during ethanol metabolism. Chen C et al. Redox Biol. 2021;46:102081.