Roles of peripheral clocks: lessons from the fly

Abstract

To adapt to and anticipate rhythmic changes in the environment such as daily light-dark and temperature cycles, internal timekeeping mechanisms called biological clocks evolved in a diverse set of organisms, from unicellular bacteria to humans. These biological clocks play critical roles in organisms' fitness and survival by temporally aligning physiological and behavioral processes to the external cues. The central clock is located in a small subset of neurons in the brain and drives daily activity rhythms, whereas most peripheral tissues harbor their own clock systems, which generate metabolic and physiological rhythms. Since the discovery of Drosophila melanogaster clock mutants in the early 1970s, the fruit fly has become an extensively studied model organism to investigate the mechanism and functions of circadian clocks. In this review, we primarily focus on D. melanogaster to survey key discoveries and progresses made over the past two decades in our understanding of peripheral clocks. We discuss physiological roles and molecular mechanisms of peripheral clocks in several different peripheral tissues of the fly.

Circadian disruption of memory consolidation in Drosophila

“…We suspect that HS- Clk jrk , loss of Pdp1ε , and DD likewise have negligible effects on sleep and circadian locomotor activity, consistent with what Inami et al reported for DD. It seems more likely that our effects are mediated by circadian involvement in “other” processes, perhaps ones that recruit “peripheral clocks” (Hardin et al, 2003 ; Ito and Tomioka, 2016 ; Sehgal, 2016 ; Di Cara and King-Jones, 2016 ; Selcho et al, 2017 ; Yildirim et al, 2022 ). Although our results do not clarify all the outstanding issues, they do provide an experimental template going forward to help resolve the current uncertainties.…”

“…The elucidation of the genes, logic, and feedback loops that constitute most eukaryotic molecular clocks has not only extended our knowledge to the mechanistic, molecular level, but reemphasized how pervasive and conserved the functions of the clock are in biology. One outstanding problem in the field is understanding the relationship between the central clock and the different “peripheral clocks” that regulate specific physiological processes (Hardin et al, 2003 ; Ito and Tomioka, 2016 ; Sehgal, 2016 ; Di Cara and King-Jones, 2016 ; Selcho et al, 2017 ; Yildirim et al, 2022 ).…”

Rhythms and Clocks in Marine Organisms

“…Circadian clocks in land organisms are the only clocks currently understood in molecular mechanistic detail. Whereas animals, plants, and fungi all rely on transcriptional/ translational feedback loops (TTFLs) for their central clock machinery, and phosphorylation/ dephosphorylation cycles play critical roles, the exact molecular factors in these three groups are not homologous or show sequence similarities only to a limited extent (Brenna & Albrecht 2020, Narasimamurthy & Virshup 2021, Saini et al 2019, Yan et al 2021, Yildirim et al 2022. Furthermore, non-TTFL-based ∼24-h oscillatory systems also exist.…”

Nutrient-sensitive protein O-GlcNAcylation shapes daily biological rhythms

“…In coordination with processes that are regulated by posttranscriptional mechanisms, clock-regulated rhythmic gene expression programs that are often tissue-and cell-specific produce daily rhythms in clock outputs. The outputs of animal circadian clocks are all-encompassing and include rhythmic processes such as sleep-wake cycles, feeding-fasting cycles, metabolism, hormone production and secretion, immune response, neuronal excitability and even permeability of the blood-brain barrier [3][4][5][6][7][8][9][10]. There is growing evidence that some clock outputs are themselves zeitgebers (i.e.…”