Multiple Functions of Peroxiredoxins: Peroxidases, Sensors and Regulators of the Intracellular Messenger H 2 O 2 , and Protein Chaperones
Abstract
Peroxiredoxins (Prxs) are a family of peroxidases that reduce peroxides, with a conserved cysteine residue (the peroxidatic Cys) serving as the site of oxidation by peroxides. Peroxides oxidize the peroxidatic Cys-SH to Cys-SOH, which then reacts with another cysteine residue (typically the resolving Cys [C(R)]) to form a disulfide that is subsequently reduced by an appropriate electron donor. On the basis of the location or absence of the C(R), Prxs are classified into 2-Cys, atypical 2-Cys, and 1-Cys Prx subfamilies. In addition to their peroxidase activity, members of the 2-Cys Prx subfamily appear to serve as peroxide sensors for other proteins and as molecular chaperones. During catalysis, the peroxidatic Cys-SOH of 2-Cys Prxs is occasionally further oxidized to Cys-SO(2)H before disulfide formation, resulting in inactivation of peroxidase activity. This hyperoxidation, which is reversed by the ATP-dependent enzyme sulfiredoxin, modulates the sensor and chaperone functions of 2-Cys Prxs. The peroxidase activity of 2-Cys Prxs is extensively regulated via tyrosine and threonine phosphorylation, which allows modulation of the local concentration of the intracellular messenger H(2)O(2). Finally, 2-Cys Prxs interact with a variety of proteins, with such interaction having been shown to modulate the function of the binding partners in a reciprocal manner.
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Based on conserved redox-sensitive Cys residues among multiple isoforms, many Prx enzymes could be oxidatively-modified and inactivated, contributing to elevated oxidative stress.
“Based on the conserved redox-sensitive Cys residues among the multiple isoforms [47], [48], [49], many Prx enzymes could be also oxidatively-modified and inactivated, contributing to elevated levels of oxidative stress.”
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- Authors
- Rhee, S. G., & Woo, H. A.
- Affiliations
- Ewha Womans University (KR)
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2011-08
- Volume
- 15
- Issue
- 3
- Pages
- 781-794
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W2153831810
- Cited by
- 463
- References
- 112
- Citations by year
- 2026: 26 · 2025: 24 · 2024: 21 · 2023: 30 · 2022: 24 · 2021: 24 · 2020: 29 · 2019: 28 · 2018: 21 · 2017: 30 · 2016: 38 · 2015: 43 · 2014: 38 · 2013: 31 · 2012: 40
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Keywords
- peroxiredoxin, 2-Cys peroxiredoxin, 1-Cys peroxiredoxin, peroxidatic cysteine, disulfide bond formation, molecular chaperones, hydrogen peroxide signaling, sulfiredoxin, hyperoxidation, phosphorylation, protein-protein interaction
- MeSH terms
- Animals, Antioxidants, Catalysis, Cysteine, Disulfides, Humans, Hydrogen Peroxide, Kinetics, Oxidation-Reduction, Peroxides, Phosphorylation, Threonine, Tyrosine, Molecular Chaperones, Peroxiredoxins
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