title: Metabolic and nontranscriptional circadian clocks: eukaryotes.
abstract: 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.
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge Metabolic Research Laboratories, National Institutes of Health Biomedical Research Center, and Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; email: areddy@cantab.net.
authors.forename: Akhilesh B
authors.initials: AB
authors.lastname: Reddy
authors.forename: Guillaume
authors.initials: G
authors.lastname: Rey
mesh_terms: D000818:Animals; D057906:Circadian Clocks; D002940:Circadian Rhythm; D000458:Cyanobacteria / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D056890:Eukaryota / Q000502:physiology*; D025461:Feedback, Physiological; D006801:Humans; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000502:physiology; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D014158:Transcription, Genetic
chemical_list: D054464:Peroxiredoxins
keywords: oscillator; oxidation-reduction; peroxiredoxin; posttranscriptional; posttranslational; redox