Circadian redox oscillations and metabolism

• Circadian rhythms adapt mammals to the daily demands associated with the day–night cycle.
• New evidence underlines the importance of non-transcriptional and metabolic oscillations in cellular timekeeping.
• Peroxiredoxin protein oxidation–reduction rhythms are a conserved marker of circadian clocks in diverse organisms including mammals.
• It is intrinsically difficult to segregate transcriptional and metabolic cycles in living systems because they are tightly coupled and interdependent.

Circadian rhythms are 24 h oscillations in physiology and behavior which allow organisms to anticipate and adapt to daily demands associated with the day/night cycle. The currently accepted model of the molecular clockwork is described as a transcriptional process composed of negative regulatory feedback loops. However, ample evidence underlines the important contribution of non-transcriptional and metabolic oscillations to cellular timekeeping. We summarize recent evidence pointing to the relationship between the transcriptional oscillator and metabolic redox state, with particular emphasis on the potential nodes of interaction. We highlight the intrinsic difficulty in segregating these two tightly coupled and interdependent processes, in living systems, and how disruption of their synchronicity impacts upon (patho)physiological processes as diverse as cardiovascular and metabolic disorders, aging, and cancer.