The circadian system as an organizer of metabolism

Abstract

The regulation of metabolism by circadian systems is believed to be a key reason for the extensive representation of circadian rhythms within the tree of life. Despite this, surprisingly little work has focused on the link between metabolism and the clock in Neurospora, a key model system in circadian research. The analysis that has been performed has focused on the unidirectional control from the clock to metabolism and largely ignored the feedback from metabolism on the clock. Recent efforts to understand these links have broken new ground, revealing bidirectional control from the clock to metabolism and vise-versa, showing just how strongly interconnected these two cellular systems can be in fungi. This review describes both well understood and emerging links between the clock and metabolic output of fungi as well as the role that metabolism plays in influencing the rhythm set by the clock.

Broad substrate-specific phosphorylation events are associated with the initial stage of plant cell wall recognition inNeurospora crassa

“…Crosstalk between gene regulation in response to different nutritional conditions and the light response pathway is extensive (Schmoll, 2018; Stappler et al, 2017) and was also shown in N. crassa (Sancar et al, 2012; Schmoll et al, 2012). FREQUENCY (FRQ; NCU02265) is a key component of the Neurospora circadian clock, allowing precise daily control of several processes, including metabolism (Hurley et al, 2016; Montenegro-Montero et al, 2015). Under day-night regimes, FRQ is known to be subjected to extensive phosphorylations (> 75 unambiguous S/T sites) throughout its daily cycle, many of which are key in determining the proper pace of the clock (Baker et al, 2009; Larrondo et al, 2015; Tang et al, 2009).…”

“…Reversible modifications in protein phosphorylation mediated by protein kinases or phosphatases represents a mechanism that is frequently employed by eukaryotic cells to transmit environmental cues and initiate signal transduction pathways, such as for transcription factor activation (Whitmarsh and Davis, 2000), cellular localization, protein stability, protein-protein interactions, DNA binding, and enzymatic activity (Breitkreutz et al, 2010; Pawson, 2007). Most cellular processes are in fact regulated by the reversible phosphorylation of proteins on serine (S), threonine (T), and tyrosine residues (Y) (Ficarro et al, 2002; Wart and Unit, 1993), including metabolism, movement, the circadian rhythms and many other (Cohen, 2000; Hurley et al, 2016; Wart and Unit, 1993).…”

The small G protein RAS2 is involved in the metabolic compensation of the circadian clock in the circadian model Neurospora crassa

“…Among these adaptation mechanisms the most intensively investigated process is temperature compensation. Although a tight interaction between metabolism and the circadian clock has been shown at almost all levels of organisms (1)(2)(3), it is still poorly understood how molecular timekeeping is compensated against changes in nutrient availability. Neurospora crassa belongs to the most extensively examined model systems in the field of circadian research and has proved to serve as a useful tool for the investigation of different aspects of circadian regulation including metabolic compensation of the circadian clock (4).…”

FlyClockbase: Importance of Biological Model Curation for Analyzing Variability in the Circadian Clock of Drosophila melanogaster by Integrating Time Series from 25 Years of Research

“…2016), including consciousness and sleep (C irelli 2009), feeding and metabolism (X u et al . 2008; H urley et al . 2016), learning and memory (X u et al .…”

“…Circadian clocks are biochemical pathways characterized by cyclical protein expression. They play a critical role in a wide variety of behavioral and physiological processes, and a better understanding of their genetic and biochemical bases could advance research in many areas (P reussner and H eyd 2016; S harma et al 2016), including consciousness and sleep (C irelli 2009), feeding and metabolism (X u et al 2008; H urley et al 2016), learning and memory (X u et al 2008; C houhan et al 2015), stress and immunity (D umbell et al 2016), inflammation (C arter et al 2016), cancer (S ephton and S piegel 2003; M asri et al 2015; S alavaty 2015; M olina -R odríguez and Á lvarez 2016), and psychological functioning (M c C lung 2013; P arekh et al 2015; C oogan et al 2016).…”