bims-ciryme 2020-02-02 papers

J Mol Biol. 2020 Jan 26. pii: S0022-2836(20)30070-X. [Epub ahead of print]

Flore Sinturel, Volodymyr Petrenko, Charna Dibner.

Most organisms adapt to the 24 hour cycle of the Earth's rotation by anticipating the time of the day through light-dark cycles. The internal time-keeping system of the circadian clocks has been developed to ensure this anticipation. The circadian system governs the rhythmicity of nearly all physiological and behavioural processes in mammals. In this review, we summarize current knowledge stemming from rodent and human studies on the tight inter-connection between the circadian system and metabolism in the body. In particular, we highlight recent advances highlighting the roles of the peripheral clocks located in the metabolic organs in regulating glucose, lipid and protein homeostasis at the organismal and cellular levels. Experimental disruption of circadian system in rodents is associated with various metabolic disturbance phenotypes. Similarly, perturbation of the clockwork in humans is linked to the development of metabolic diseases. We discuss recent studies that reveal roles of the circadian system in the temporal coordination of metabolism under physiological conditions and in the development of human pathologies.

Keywords: Circadian clock system; circadian misalignment; human pathologies; metabolic rhythms

DOI: https://doi.org/10.1016/j.jmb.2020.01.018

Nat Commun. 2020 Jan 30. 11(1): 589

The tight junction protein TJP1 regulates the feeding-modulated hepatic circadian clock.

Yi Liu, Yuanyuan Zhang, Tong Li, Jinbo Han, Yiguo Wang.

Circadian clocks in the suprachiasmatic nucleus and peripheral tissues orchestrate behavioral and physiological activities of mammals in response to environmental cues. In the liver, the circadian clock is also modulated by feeding. However, the molecular mechanisms involved are unclear. Here, we show that TJP1 (tight junction protein 1) functions as a mediator of mTOR (mechanistic target of rapamycin) to modulate the hepatic circadian clock. TJP1 interacts with PER1 (period circadian regulator 1) and prevents its nuclear translocation. During feeding, mTOR phosphorylates TJP1 and attenuates its association with PER1, thereby enhancing nuclear shuttling of PER1 to dampen circadian oscillation. Therefore, our results provide a previously uncharacterized mechanistic insight into how feeding modulates the hepatic circadian clock.

DOI: https://doi.org/10.1038/s41467-020-14470-2

Trends Cell Biol. 2020 Jan 23. pii: S0962-8924(19)30219-3. [Epub ahead of print]

Metabolic Regulation of Cell Fate and Function.

Shohini Ghosh-Choudhary, Jie Liu, Toren Finkel.

Increasing evidence implicates metabolic pathways as key regulators of cell fate and function. Although the metabolism of glucose, amino acids, and fatty acids is essential to maintain overall energy homeostasis, the choice of a given metabolic pathway and the levels of particular substrates and intermediates increasingly appear to modulate specific cellular activities. This connection is likely related to the growing appreciation that molecules such as acetyl-CoA act as a shared currency between metabolic flux and chromatin modification. We review recent evidence for a role of metabolism in modulating cellular function in four distinct contexts. These areas include the immune system, the tumor microenvironment, the fibrotic response, and stem cell function. Together, these examples suggest that metabolic pathways do not simply provide the fuel that powers cellular activities but instead help to shape and determine cellular identity.

DOI: https://doi.org/10.1016/j.tcb.2019.12.005