Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxin

N_03_Sue-Goo Rhee(photo)
Sue Goo Rhee
Yonsei University College of Medicine

Abstract :

Despite its inherent toxicity, H2O2 is produced in a regulated fashion by many mammalian cell types as a signaling molecule that mediates numerous biological responses. H2O2 is distinct from other messenger molecules, however, in that it acts not by binding to effectors but by oxidizing their critical residues, most notably Cys, as exemplified by the inhibition of protein tyrosine phosphatases. For H2O2 to oxidize target Cys residues, its concentration must increase above a certain threshold and remain elevated long enough to achieve the relatively slow oxidation reaction in the presence of H2O2-eliminating enzymes like catalase, glutathione peroxidases, and peroxiredoxins (Prxs).


Prxs constitute a large family of thiol-dependent peroxidases that catalyze the reduction of H2O2) and contain a conserved Cys residue that undergoes a cycle of peroxide-dependent oxidation and thiol-dependent reduction during catalysis. Mammalian cells express six isoforms of Prx (Prx I to VI). Prxs are abundant proteins and their catalytic cysteine reacts several orders of magnitude faster with H2O2 than do the catalytic cysteines of H2O2-target proteins.


Given that these effector proteins are at such a competitive disadvantage, it seems likely that neighboring Prx molecules must be transiently inactivated in order to allow the effectors to react with H2O2. Examples of such a scenario include inactivation of PrxI through its phosphorylation by protein tyrosine kinases of the Src family at the plasma membrane or through its phosphorylation by cyclin B–dependent kinase at the centrosome and inactivation of PrxIII through reversible hyperoxidation of catalytic cysteine in mitochondria. Such localized regulation of Prx thus allows H2O2 to accumulate in specific regions of the cell without global redox disturbance.In some instances, redox-regulated proteins are not directly oxidized by H2O2, with their oxidation instead being mediated by Prxs. In this scenario, Prx is first oxidized by H2O2 and then transfers its oxidation state to a redox-regulated protein, thus serving as both a sensor and transducer of H2O2 signaling.



1965 B.S. Chemistry, Seoul National University, Seoul, Korea
1972 Ph.D. Organic Chemistry, Catholic University of America, Washington, DC


Awards & Honors

  • 2014 Oxygen Society of California and Jarrow Health Sciences Prize
  • 2011 Chungsan Award, Korean Society for Biochemistry and Molecular Biology
  • 2006 Elected to the First National Honor Scientist of Korea
  • 2005 Discovery Award, The society of Free Radical Biology and Medicine
  • 2004 NIH Outstanding Mentor Award
  • 2003 Scientific Leadership Recognition awarded by the Oxygen Club of Washington DC
  • 2001 Faculty 1000
  • 1995 Ho Am (Sam Sung)Award in Science
  • 1992 Biomega Lectureship Award
  • 1991 NIH Director’s Award
  • 1990 Pfizer Lectureship Award


Professional Activities

  • 2015-present Distinguished Editorial Board member, Free Radicals in Biology and Medicine
  • 2013-present Newilhan Professor of Biomedical Research, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
  • 2008-2014 Editorial Board member, Free Radicals in Biology and Medicine
  • 2007-2011 Editor-in-chief, Molecules and Cells
  • 2006-2011 Editorial Board member, The Journal of Biological Chemistry
  • 2005-2013 Distinguished Professor, Division of Life and Pharmaceutical Sciences Director, Institute of Molecular Life Science and Technology, Ewha Woman’s University
  • 1998-2003 Editor, Current Topics in Cellular Regulation
  • 1998-2003 Editorial Board member, The Journal of Biological Chemistry
  • 1994-2005 Chief, Laboratory of Cell Signaling, NHLBI, NIH
  • 1993-2011 Editorial Advisory Board, Molecules and Cells
  • 1992-1997 Editorial Advisory Panel, The Biochemical Journal
  • 1991-1998 Editorial Board member, BioFactors
  • 1991-1995 Editorial Board member, The Journal of Biological Chemistry
  • 1973-1994 Postdoctoral, Staff Fellow, Senior Scientist, Chief of the Section on Signal Transduction, Laboratory of Biochemistry, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH) Bethesda, MD
  • 1971-1972 Postdoctoral Fellow, The Catholic University of America and the State University of New York