Modeling reveals temperature compensation and entrainment in the peroxiredoxin-based redox oscillator as an ancient circadian timekeeper

Mar 13, 2026Physical biology

Modeling shows temperature balance and daily rhythm syncing in a cell’s ancient redox clock

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Abstract

The peroxiredoxin redox oscillator exhibits temperature-compensated periodicity and can be entrained by external signals.

Peroxiredoxins display approximately 24-hour redox-state oscillations across various species.
These oscillations operate independently of traditional transcription-translation feedback mechanisms.
A mathematical model accurately reproduced redox oscillations in plants, fruit flies, and mice using physiological parameters.
The model indicates that the redox oscillator has a largely temperature-invariant inverse angular speed, supporting period stability.
Phase response curves suggest that the oscillator experiences phase-dependent shifts and can robustly synchronize with environmental cues.

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Peroxiredoxins (PRXs) are antioxidant enzymes that exhibit ∼24-hour redox-state oscillations across diverse life forms. These non-transcriptional rhythms operate independently of the canonical transcription-translation feedback loops, suggesting an ancient, conserved timekeeping mechanism. However, whether this redox oscillator meets the core circadian criteria-entrainment and temperature compensationremains a key question. To address this, we developed and calibrated a mathematical model of the mitochondrial PRX/SRX/TRX redox cycle using physiologically meaningful parameters. The model quantitatively reproduced experimental redox oscillations in A. thaliana, D. melanogaster, and M. musculus. Simulations revealed that the PRX redox oscillator possesses both temperature-compensated periodicity and the capacity for entrainment by periodic thermal and oxidative signals, thereby fulfilling the core criteria of a circadian clock. The inverse angular speed, when integrated over the closed orbit, is largely temperature-invariant, thus providing a mathematical basis for the observed period stability. The calculated phase response curves, which show phase-dependent shifts, together with the broad Arnold tongue for 1:1 resonance, demonstrate a substantial entrainment range that enables the internal rhythm to robustly lock onto periodic environmental Zeitgebers. Implications: Our findings suggest that the peroxiredoxin redox oscillator meets the criteria for a circadian clock: it can be entrained by external cues and its periodicity is temperature-compensated.

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Modeling reveals temperature compensation and entrainment in the peroxiredoxin-based redox oscillator as an ancient circadian timekeeper

Abstract

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