Molecular mechanisms of the circadian clockwork in mammals

Circadian rhythms enable organisms to co-ordinate biological processes with the predictable 24 h cycle of day and night. Given that molecular clocks that coordinate such biological timing have evolved in almost all organisms, it is clear that being synchronous with the external environment confers competitive advantage. Conversely, it is apparent that being out of phase is detrimental, resulting in a number of clinical conditions, many of which are linked to metabolic dysfunction. The canonical clockwork involves a core set of genes that negatively regulate themselves through a so-called transcription translation feedback loop. However, recent studies describing evolutionarily conserved oscillations in redox reactions link circadian rhythms to metabolic processes, and in particular, redox pathways. In this review we describe the evidence for the interaction between transcriptional loops, redox and metabolism in mammals and suggest the clock may be potential target for the treatment of disease.