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Updated: Jul 16, 2025

Rapid Analysis of Circadian Phenotypes in Arabidopsis Protoplasts Transfected with a Luminescent Clock Reporter
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The Case for the Target of Rapamycin Pathway as a Candidate Circadian Oscillator

Patricia Lakin-Thomas1

  • 1Department of Biology, York University, Toronto, ON M3J 1P3, Canada.

International Journal of Molecular Sciences
|September 9, 2023
PubMed

Insights

The Target of Rapamycin (TOR) signaling pathway may drive circadian rhythms independently of transcription/translation feedback loops (TTFLs). This review explores TOR as a potential non-TTFL oscillator in eukaryotic circadian systems.

Area of Science:

  • Molecular Biology
  • Chronobiology
  • Metabolic Regulation

Background:

  • Eukaryotic circadian systems are complex, with transcription/translation feedback loops (TTFLs) being the primary model.
  • Circadian rhythms persist even when TTFLs are non-functional, indicating the existence of alternative oscillators.
  • The molecular basis for these non-TTFL circadian oscillators remains largely unknown.

Purpose of the Study:

  • To review evidence supporting the Target of Rapamycin (TOR) signaling pathway as a candidate for a non-TTFL circadian oscillator.
  • To discuss the advantages of TOR as a potential driver of circadian rhythmicity.
  • To explore potential mechanisms for TOR-driven oscillations and identify future research directions.

Main Methods:

  • Literature review of evidence linking TOR signaling to circadian rhythmicity.
  • Analysis of TOR's role as a metabolic regulator in eukaryotes.
  • Comparison with known ultradian metabolic cycles, such as those in yeast.

Main Results:

  • The TOR signaling pathway, a key regulator of eukaryotic metabolism, is increasingly linked to circadian research.
  • Extensive feedback regulation within the TOR pathway suggests plausible mechanisms for self-sustained oscillations.
  • Ultradian yeast metabolic cycles serve as a model for potential TOR-driven oscillations.

Conclusions:

  • The TOR signaling pathway presents a compelling candidate for a non-TTFL oscillator driving circadian rhythms.
  • TOR's central role in metabolism and its regulatory feedback loops offer a framework for understanding non-TTFL rhythmicity.
  • Further research is needed to elucidate the precise mechanisms and validate TOR's role in eukaryotic circadian systems.
Keywords:
NeurosporaTarget of Rapamycincircadianmetabolismyeast metabolic cycles

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