Is redox metabolism connected with Circadian Rhythm?

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by Carolina Gonçalves Fernandes

Circadian Rhythm is any biological process that temporally organizes behavioral, physiological, and molecular events around the 24h day-night cycle. This process has evolved over approximately 2.5 billion years ago at the Great Oxidation Event. The later involved increases in atmospheric oxygen levels that simulatenwously enabled organisms to resonate with their environment such that their internal cycles anticipate and match external rhythms on Earth. In mammals, this rhythmicity is controlled by the hypothalamic suprachiasmatic nuclei (SCN) receiving retina signals and “translating” them into each tissue/organ that commonly responds using the transcription/translation feedback loop (TTFL) mechanisms (activating or inhibiting gene transcription). However, recent investigations demonstrated that TTFL pathways are not the only mechanisms to coordinate circadian clocks and point to a role for redox processes in these effects. Specifically, Many of those mechanisms are linked to TTFL pathways and include NAD+ oscillations, which control the rate-limiting enzyme in the NAD+ salvage pathway via feedback mechanisms. In addition, other energy/redox metabolites also oscillate in mammals in a circadian fashion, such as glutathione, NAD(P)H and ATP, also through TTFL mechanisms. However, peroxiredoxins (PRX) also oscillate in circadian rhythm in a highly conserved fashion, since Archea to humans, but even in enucleated cells. Furthermore, peroxiredoxin oscillations persist even in red blood cells, reinforcing the existence of non-TTFL circadian regulation mechanism. The importance of redox circuits in circadian clock regulation fits well with the fact that disturbance in these rhythms is linked to pathological processes such as aging, neurodegenerative disorders, cancer and various metabolic conditions [1], in which redox processes have been proposed to play a significant role.


  1. N. B. Milev and A. B. Reddy.
    Circadian redox oscillations and metabolism.
    Trends in Endocrinology & Metabolism, 26: 430-7, 2015 | doi:10.1016/j.tem.2015.05.012

Contributed by Carolina Gonçalves Fernandes, post-doc at the Francisco Laurindo Lab, Heart Institute, University of São Paulo School of Medicine.

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