驱动昼夜节律(24小时)节律的分子机制已经研究了几十年,但是我们仍然没有完整的真核生物昼夜节律系统。尽管转录/翻译反馈环(TTFL)模型一直是研究的主要焦点,当TTFL不起作用时,有许多昼夜节律持续存在的例子,我们缺乏驱动这些节奏的非TTFL振荡器的好人选。在这篇假设驱动的评论中,作者汇集了几条证据,指出雷帕霉素靶蛋白(TOR)信号通路是非TTFL振荡器的良好候选者。TOR是真核生物中普遍存在的代谢调节剂,最近对代谢和节律之间联系的昼夜节律研究的关注使TOR成为有吸引力的候选振荡器。在本文中,回顾了TOR在调节节律中的作用的证据,并讨论了TOR作为潜在振荡器的优势。TOR的广泛反馈调节的证据为TOR驱动的振荡器提供了潜在的机制。与超日酵母代谢循环的比较提供了潜在的TOR驱动的自持振荡的示例。讨论了未解决的问题和未来研究要解决的问题。
The molecular mechanisms that drive circadian (24 h) rhythmicity have been investigated for many decades, but we still do not have a complete picture of eukaryotic circadian systems. Although the transcription/translation feedback loop (TTFL) model has been the primary focus of research, there are many examples of circadian rhythms that persist when TTFLs are not functioning, and we lack any good candidates for the non-TTFL oscillators driving these rhythms. In this hypothesis-driven review, the author brings together several lines of evidence pointing towards the Target of Rapamycin (TOR) signalling pathway as a good candidate for a non-TTFL oscillator. TOR is a ubiquitous regulator of metabolism in eukaryotes and recent focus in circadian research on connections between metabolism and rhythms makes TOR an attractive candidate oscillator. In this paper, the evidence for a role for TOR in regulating rhythmicity is reviewed, and the advantages of TOR as a potential oscillator are discussed. Evidence for extensive feedback regulation of TOR provides potential mechanisms for a TOR-driven oscillator. Comparison with ultradian yeast metabolic cycles provides an example of a potential TOR-driven self-sustained oscillation. Unanswered questions and problems to be addressed by future research are discussed.