Editors' ChoiceRedox Signaling

Regulating Hydrogen Peroxide Signaling

Science's STKE  29 Apr 2003:
Vol. 2003, Issue 180, pp. tw172-TW172
DOI: 10.1126/stke.2003.180.tw172

Hydrogen peroxide (H2O2) is both a source of oxidative stress and a second messenger in signal transduction. Two reports provide insight into how 2-cys peroxiredoxins (Prxs) can both reduce H2O2 and regulate H2O2 signaling (see the Perspective by Georgious and Masip). Wood et al. show that eukaryotic 2-Cys Prxs have structural features not present in bacterial Prxs that make them sensitive to inactivation by overoxidation of the peroxidatic cysteine to the sulfinic acid form. They suggest that this capacity for inactivation has evolved so that 2-Cys Prxs function as a floodgate--signaling is blocked until there is a burst in the H2O2 concentration that is sufficient to inactivate 2-Cys Prx and open the floodgate. Oxidation of cysteine to sulfinic acid was thought to be irreversible in cells. However, Woo et al. show that in mammalian cells the sulfinic form of periredoxin I is rapidly reduced back to the catalytically active thiol form. The reversibility of this reaction is consistent with its possible involvement in the regulation of H2O2 signaling.

G. Georgiou, L. Masip, An overoxidation journey with a return ticket. Science 300, 592-594 (2003). [Summary] [Full Text]

Z. A. Wood, L. B. Poole, P. A. Karplus, Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300, 650-653 (2003). [Abstract] [Full Text]

H. A. Woo, H. Z. Chae, S. C. Hwang, K.-S. Yang, S. W. Kang, K. Kim, S. Goo Rhee, Reversing the inactivation of peroxiredoxins caused by cysteine sulfinic acid formation. Science 300, 653-656 (2003). [Abstract][Full Text]