Circadian redox oscillations and metabolism

Abstract

Circadian rhythms are 24h 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.

Cancer and the Circadian Clock

“…Coordinated interaction between the molecular circadian clock and the intricate network of metabolic pathways is required for maintenance of physiologic homeostasis in healthy cells. First identified in mammalian red blood cells (91), the metabolic circadian clock is independent of transcriptional activity and is sustained through the redox cycle of peroxiredoxin/thioredoxin/NADPH enzymes (92)(93)(94). This complex displays a 24-hour redox fluctuation metabolizing H 2 O 2 in various tissues throughout the body.…”

Cellular Timekeeping: It’s Redox o’Clock

“…One of the emerging concepts in the past couple of decades is that the circadian system shows pronounced tissue-specific roles. Indeed, the importance of the cellular redox state in the generation of tissue-specific oscillations has been shown for most major organ systems (Milev and Reddy 2015).…”

The pathogenesis of obesity

“…Most metabolically active cells also have an internal, peripheral clock that enables tissues to regulate gene expression locally in an autonomic manner [225][226][227][228]. The central clock is primarily synchronized by afferent signals from the retina [229,230], but fine-tuned in response to other signals such as meal timing and food composition [231,232]. Peripheral clocks, in turn, are synchronized by signals from the SCN and have several mechanisms to influence metabolism, including circulating levels of hormones and metabolites.…”