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.
