Metabolic and nontranscriptional circadian clocks: eukaryotes

Annu Rev Biochem. 2014:83:165-89. doi: 10.1146/annurev-biochem-060713-035623. Epub 2014 Mar 3.


Circadian clocks are cellular timekeeping mechanisms that coordinate behavior and physiology around the 24-h day in most living organisms. Misalignment of an organism's clock with its environment is associated with long-term adverse fitness consequences, as exemplified by the link between circadian disruption and various age-related diseases in humans. Current eukaryotic models of the circadian oscillator rely on transcription/translation feedback loop mechanisms, supplemented with accessory cytosolic loops that connect them to cellular physiology. However, mounting evidence is questioning the absolute necessity of transcription-based oscillators for circadian rhythmicity, supported by the recent discovery of oxidation-reduction cycles of peroxiredoxin proteins, which persist even in the absence of transcription. A more fundamental mechanism based on metabolic cycles could thus underlie circadian transcriptional and cytosolic rhythms, thereby promoting circadian oscillations to integral properties of cellular metabolism.

Keywords: oscillator; oxidation-reduction; peroxiredoxin; posttranscriptional; posttranslational; redox.

Publication types

  • Review

MeSH terms

  • Animals
  • Circadian Clocks*
  • Circadian Rhythm*
  • Cyanobacteria / metabolism
  • Cytosol / metabolism
  • Eukaryota / physiology*
  • Feedback, Physiological
  • Humans
  • Oxidation-Reduction
  • Peroxiredoxins / physiology
  • Protein Processing, Post-Translational
  • RNA Processing, Post-Transcriptional
  • Transcription, Genetic*


  • Peroxiredoxins