Circadian Redox and Metabolic Oscillations in Mammalian Systems
Open accessAbstract
Significance: A substantial proportion of mammalian physiology is organized around the day/night cycle, being regulated by the co-ordinated action of numerous cell-autonomous circadian oscillators throughout the body. Disruption of internal timekeeping, by genetic or environmental perturbation, leads to metabolic dysregulation, whereas changes in metabolism affect timekeeping. Recent Advances: While gene expression cycles are essential for the temporal coordination of normal physiology, it has become clear that rhythms in metabolism and redox balance are cell-intrinsic phenomena, which may regulate gene expression cycles reciprocally, but persist in their absence. For example, a circadian rhythm in peroxiredoxin oxidation was recently observed in isolated human erythrocytes, fibroblast cell lines in vitro , and mouse liver in vivo . Critical Issues: Mammalian timekeeping is a cellular phenomenon. While we understand many of the cellular systems that contribute to this biological oscillation's fidelity and robustness, a comprehensive mechanistic understanding remains elusive. Moreover, the formerly clear distinction between “core clock components” and rhythmic cellular outputs is blurred since several outputs, for example, redox balance, can feed back to regulate timekeeping. As with any cyclical system, establishing causality becomes problematic. Future Directions: A detailed molecular understanding of the temporal crosstalk between cellular systems, and the coincidence detection mechanisms that allow a cell to discriminate clock-relevant from irrelevant stimuli, will be essential as we move toward an integrated model of how this daily biological oscillation works. Such knowledge will highlight new avenues by which the functional consequences of circadian timekeeping can be explored in the context of human health and disease. Antioxid. Redox Signal. 20, 2966–2981.
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Elements of the molecular circadian clock directly regulate cellular metabolism and mitochondrial function in the liver and other tissues.
“Recent studies have demonstrated that elements of the molecular circadian clock directly regulate cellular metabolism and mitochondrial function in the liver and other tissues316–318.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [317]
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Ji, Z., Shang, D., Kim, P., Yang, M., Wu, S., Zhao, W., Kim, E., Wirianto, M., Chen, Z., Yoo, S. H., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.16.207357
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Mitochondria, neurosteroids and biological rhythms : implications in health and disease states
Grimm, A. (2015) · theses.fr (ABES) · doi:10.70675/8aac5aa9z77cdz49bdz9cf5z0ff0b5dd0f84
Karim, Z., Guha, L., Manna, P., Anjan Gowda, B. H., Gupta, A. K., & Hakeem, K. R. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12675-0
- Authors
- O'Neill, J. S., & Feeney, K. A.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2014-06
- Volume
- 20
- Issue
- 18
- Pages
- 2966-2981
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC4038991
- OpenAlex
- W2030605788
- Cited by
- 51
- References
- 145
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 9 · 2017: 2 · 2016: 4 · 2015: 6 · 2014: 1
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antioxidants and Redox Signaling (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (093734/Z/10/Z)
- Medical Research Council (MC_UP_1201/4)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- circadian clock, redox oscillations, metabolic oscillations, circadian gene expression, metabolic dysfunction, coincidence detection, redox signaling
- MeSH terms
- Animals, Biological Clocks, Circadian Rhythm, Gene Expression Regulation, Humans, Mammals, Metabolism, Oxidation-Reduction, Mice, Circadian Clocks
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