Circadian redox oscillations and metabolism

Milev, N; Reddy, Akhilesh B.

doi:10.1016/j.tem.2015.05.012

Cited by 56 publications

(37 citation statements)

References 81 publications

(109 reference statements)

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“…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.…”

Section: Mechanisms Linking Clock Dysfunction To the Hallmarks Of Cancermentioning

confidence: 99%

Cancer and the Circadian Clock

2019

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The circadian clock is a master regulator of mammalian physiology, regulating daily oscillations of crucial biological processes and behaviors. Notably, circadian disruption has recently been identified as an independent risk factor for cancer and classified as a carcinogen. As such, it is imperative to discern the underpinning mechanisms by which circadian disruption alters cancer risk. Emergent data, reviewed herein , demonstrate that circadian regulatory functions play critical roles in several hallmarks of cancer, including control of cell proliferation, cell death, DNA repair, and metabolic alteration. Developing a deeper understanding of circadian-cancer regulation cross-talk holds promise for developing new strategies for cancer interception, prevention, and management.

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Section: Mechanisms Linking Clock Dysfunction To the Hallmarks Of Cancermentioning

confidence: 99%

Cancer and the Circadian Clock

2019

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“…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).…”

Section: The Cellular Redox Poise and Circadian Timekeeping: A Systemmentioning

confidence: 99%

Cellular Timekeeping: It’s Redox o’Clock

Milev

Rhee

Reddy

2017

Cold Spring Harb Perspect Biol

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Mounting evidence in recent years supports the extensive interaction between the circadian and redox systems. The existence of such a relationship is not surprising because most organisms, be they diurnal or nocturnal, display daily oscillations in energy intake, locomotor activity, and exposure to exogenous and internally generated oxidants. The transcriptional clock controls the levels of many antioxidant proteins and redox-active cofactors, and, conversely, the cellular redox poise has been shown to feed back to the transcriptional oscillator via redox-sensitive transcription factors and enzymes. However, the circadian cycles in the -sulfinylation of the peroxiredoxin (PRDX) proteins constituted the first example of an autonomous circadian redox oscillation, which occurred independently of the transcriptional clock. Importantly, the high phylogenetic conservation of these rhythms suggests that they might predate the evolution of the transcriptional oscillator, and therefore could be a part of a primordial circadian redox/metabolic oscillator. This discovery forced the reappraisal of the dogmatic transcription-centered view of the clockwork and opened a new avenue of research. Indeed, the investigation into the links between the circadian and redox systems is still in its infancy, and many important questions remain to be addressed.

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“…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.…”

Section: Circadian Rhythmsmentioning

confidence: 99%