bims-ciryme 2019-12-29 papers

Issue of 2019‒12‒29
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

Sci Rep. 2019 Dec 27. 9(1): 20114

Differentiating external zeitgeber impact on peripheral circadian clock resetting.

Circadian clocks regulate physiological functions, including energy metabolism, along the 24-hour day cycle. The mammalian clock system is organized in a hierarchical manner with a coordinating pacemaker residing in the hypothalamic suprachiasmatic nucleus (SCN). The SCN clock is reset primarily by the external light-dark cycle while other zeitgebers such as the timing of food intake are potent synchronizers of many peripheral tissue clocks. Under conflicting zeitgeber conditions, e.g. during shift work, phase synchrony across the clock network is disrupted promoting the development of metabolic disorders. We established a zeitgeber desynchrony (ZD) paradigm to quantify the differential contributions of the two main zeitgebers, light and food, to the resetting of specific tissue clocks and the effect on metabolic homeostasis in mice. Under 28-hour light-dark and 24-hour feeding-fasting conditions SCN and peripheral clock, as well as activity and hormonal rhythms showed specific periodicities aligning in-between those of the two zeitgebers. During ZD, metabolic homeostasis was cyclic with mice gaining weight under synchronous and losing weight under conflicting zeitgeber conditions. In summary, our study establishes an experimental paradigm to compare zeitgeber input in vivo and study the physiological consequences of chronodisruption.

DOI: https://doi.org/10.1038/s41598-019-56323-z

Proc Natl Acad Sci U S A. 2019 Dec 26. pii: 201913712. [Epub ahead of print]

Spatiotemporal regulation of NADP(H) phosphatase Nocturnin and its role in oxidative stress response.

Isara Laothamatas, Peng Gao, Anushka Wickramaratne, Carlo G Quintanilla, Arianna Dino, Crystal A Khan, Jen Liou, Carla B Green.

An intimate link exists between circadian clocks and metabolism with nearly every metabolic pathway in the mammalian liver under circadian control. Circadian regulation of metabolism is largely driven by rhythmic transcriptional activation of clock-controlled genes. Among these output genes, Nocturnin (Noct) has one of the highest amplitude rhythms at the mRNA level. The Noct gene encodes a protein (NOC) that is highly conserved with the endonuclease/exonuclease/phosphatase (EEP) domain-containing CCR4 family of deadenylases, but highly purified NOC possesses little or no ribonuclease activity. Here, we show that NOC utilizes the dinucleotide NADP(H) as a substrate, removing the 2' phosphate to generate NAD(H), and is a direct regulator of oxidative stress response through its NADPH 2' phosphatase activity. Furthermore, we describe two isoforms of NOC in the mouse liver. The cytoplasmic form of NOC is constitutively expressed and associates externally with membranes of other organelles, including the endoplasmic reticulum, via N-terminal glycine myristoylation. In contrast, the mitochondrial form of NOC possesses high-amplitude circadian rhythmicity with peak expression level during the early dark phase. These findings suggest that NOC regulates local intracellular concentrations of NADP(H) in a manner that changes over the course of the day.

Keywords: NADPH; Nocturnin; circadian; mitochondria; oxidative stress

DOI: https://doi.org/10.1073/pnas.1913712117