CTP synthase (CTPS), the rate-limiting enzyme in de novo CTP biosynthesis, has been demonstrated to assemble into evolutionarily conserved filamentous structures, termed cytoophidia, in Drosophila, bacteria, yeast and mammalian cells. However, the regulation and function of the cytoophidium remain elusive. Here, we provide evidence that the mechanistic target of rapamycin (mTOR) pathway controls cytoophidium assembly in mammalian and Drosophila cells. In mammalian cells, we find that inhibition of mTOR pathway attenuates cytoophidium formation. Moreover, CTPS cytoophidium assembly appears to be dependent on the mTOR complex 1 (mTORC1) mainly. In addition, knockdown of the mTORC1 downstream target S6K1 can inhibit cytoophidium formation, while overexpression of the constitutively active S6K1 reverses mTOR knockdown-induced cytoophidium disassembly. Finally, reducing mTOR protein expression results in a decrease of the length of cytoophidium in Drosophila follicle cells. Therefore, our study connects CTPS cytoophidium formation with the mTOR signaling pathway.

CTP 合酶 (CTPS) 是从头CTP 生物合成中的限速酶，已被证明在果蝇、细菌、酵母和哺乳动物细胞中组装成进化上保守的丝状结构，称为细胞毒。然而，细胞毒的调节和功能仍然难以捉摸。在这里，我们提供证据表明，雷帕霉素 (mTOR) 途径的机械靶点控制哺乳动物和果蝇中的 cytoophidium 组装细胞。在哺乳动物细胞中，我们发现抑制 mTOR 途径会减弱细胞毒的形成。此外，CTPS cytoophidium 组装似乎主要依赖于 mTOR 复合物 1 (mTORC1)。此外，mTORC1 下游靶标 S6K1 的敲低可以抑制细胞毒的形成，而组成型活性 S6K1 的过表达可逆转 mTOR 敲低诱导的细胞毒分解。最后，降低 mTOR 蛋白表达会导致果蝇滤泡细胞中的胞浆长度减少。因此，我们的研究将 CTPS cytoophidium 的形成与 mTOR 信号通路联系起来。