Crosstalk between the circadian clock clockwork and cellular metabolic regulatory networks is crucial to ensure an adequate response of an organism to the day/night cycle. mTOR (mammalian/mechanistic target of rapamycin) is a master growth regulator and sensor of nutrient status, which is part of the mTOR complex 1 (mTORC1). While the circadian clock confers rhythmicity to the mTOR protein by regulating its degradation rate, mTORC1 activity diminishes period and augments amplitude of circadian oscillations at the cellular level by a currently unknown mechanism. Here, we develop a mathematical deterministic DAE (differential–algebraic equation) model, to explore the possible interactions that allow mTORC1 to display such regulation of the core circadian clock. Our results suggest that mTORC1 is capable of regulating amplitude by exerting translational control on core the clock protein BMAL1, and that period-tuning is achieved by controlling post-translational localization of BMAL1. Since, in our model, mTORC1 control of BMAL1 localization greatly diminishes the ability of the clock to oscillate, and regulation of BMAL1 translation reduces this effect, our results also suggest that both levels of regulation must be present to ensure the robustness of oscillations. Together, the above results emphasize the importance of the influence of mTORC1 on the circadian rhythms.

昼夜节律时钟与细胞代谢调节网络之间的串扰对于确保生物体对昼/夜周期的充分响应至关重要。mTOR（雷帕霉素的哺乳动物/机械靶标）是主要的生长调节剂和营养状态传感器，它是mTOR复合物1（mTORC1）的一部分。尽管昼夜节律时钟通过调节mTOR蛋白的降解速率赋予其节律性，但mTORC1的活性降低了周期，并通过目前未知的机制在细胞水平上增加了昼夜节律振荡的幅度。在这里，我们开发了数学确定性DAE（微分-代数方程）模型，以探索可能的相互作用，使mTORC1显示核心生物钟的这种调节。我们的结果表明，mTORC1能够通过在时钟蛋白BMAL1的核心上施加翻译控制来调节幅度，并且通过控制BMAL1的翻译后定位来实现周期调整。由于在我们的模型中，mTORC1对BMAL1定位的控制极大地降低了时钟振荡的能力，而BMAL1翻译的调节降低了这种影响，因此我们的结果还表明，必须同时存在两种调节水平，才能确保振荡的鲁棒性。在一起，以上结果强调了mTORC1对昼夜节律的影响的重要性。mTORC1对BMAL1定位的控制大大降低了时钟振荡的能力，而BMAL1翻译的调节降低了这种影响，我们的结果还表明必须同时存在两种调节水平，以确保振荡的鲁棒性。在一起，以上结果强调了mTORC1对昼夜节律的影响的重要性。mTORC1对BMAL1定位的控制极大地降低了时钟振荡的能力，而BMAL1翻译的调节降低了这种影响，我们的结果还表明必须同时存在两种调节水平，以确保振荡的鲁棒性。在一起，以上结果强调了mTORC1对昼夜节律的影响的重要性。