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Fundamentals of redox regulation in biology

An Author Correction to this article was published on 17 June 2024

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Abstract

Oxidation–reduction (redox) reactions are central to the existence of life. Reactive species of oxygen, nitrogen and sulfur mediate redox control of a wide range of essential cellular processes. Yet, excessive levels of oxidants are associated with ageing and many diseases, including cardiological and neurodegenerative diseases, and cancer. Hence, maintaining the fine-tuned steady-state balance of reactive species production and removal is essential. Here, we discuss new insights into the dynamic maintenance of redox homeostasis (that is, redox homeodynamics) and the principles underlying biological redox organization, termed the ‘redox code’. We survey how redox changes result in stress responses by hormesis mechanisms, and how the lifelong cumulative exposure to environmental agents, termed the ‘exposome’, is communicated to cells through redox signals. Better understanding of the molecular and cellular basis of redox biology will guide novel redox medicine approaches aimed at preventing and treating diseases associated with disturbed redox regulation.

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Fig. 1: Principles of redox regulation.
Fig. 2: Redox eustress and transition to oxidative and reductive distress.
Fig. 3: Schematic overview of redox communication in and between cells.
Fig. 4: Major cellular processes under redox regulation.

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Acknowledgements

The authors are grateful to D. P. Jones, a longtime friend and colleague, for his substantial input and advice. B. Oleson helped with preparing figures. The authors also thank many researchers active in redox biology, who have generated an impressive literature that could not be covered exhaustively in the present overview. H.S. acknowledges longstanding support by Deutsche Forschungsgemeinschaft, Bonn, Germany, and by the National Foundation for Cancer Research, Bethesda, MD, USA. R.J.M. acknowledges Natural Sciences and Engineering Research Council of Canada Discovery Grant Program (RGPIN-2022-03240). U.J. acknowledges the National Institute of Health grant R35 GM122506 and the National Institute of Aging grant R21 AG078540.

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Glossary

Antioxidants

Any substance that prevents, delays or removes oxidative damage. In biology, this includes various antioxidant enzymes and low-molecular-weight antioxidant compounds.

Hormesis

This term describes a biphasic dose–response phenomenon, whereby low-dose exposure leads to stimulation or preconditioning and high-dose exposure causes inhibition. The phenomenon is often described by a J-shaped or inverted U-shaped dose–response curve.

Oxidative distress

Biomolecular damage upon supraphysiological exposure to oxidants, resulting in detrimental consequence to life processes.

p53 pathway

A tumour suppression pathway, which oversees cell cycle regulation, DNA repair and cell death mechanisms to halt the proliferation of aberrant cells.

Redox stress signalling threshold

(RST). Condition at which the oxidant or reductant load causes the transition from beneficial (eustress) to detrimental (distress) outcome.

Surface-enhanced Raman spectroscopy

(SERS). A surface-sensitive method that amplifies Raman scattering from molecules absorbed on metal surfaces or nanostructures.

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Sies, H., Mailloux, R.J. & Jakob, U. Fundamentals of redox regulation in biology. Nat Rev Mol Cell Biol (2024). https://doi.org/10.1038/s41580-024-00730-2

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