Background Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo GTP biosynthesis, plays an important role in cell metabolism and proliferation. It has been demonstrated that IMPDH can aggregate into a macrostructure, termed the cytoophidium, in mammalian cells under a variety of conditions. However, the regulation and function of the cytoophidium are still elusive. Results In this study, we report that spontaneous filamentation of IMPDH is correlated with rapid cell proliferation. Intracellular IMP accumulation promoted cytoophidium assembly, whereas elevated GTP level triggered disassociation of aggregates. By using IMPDH2 CBS domain mutant cell models, which are unable to form the cytoophidium, we have determined that the cytoophidium is of the utmost importance for maintaining the GTP pool and normal cell proliferation in the condition that higher IMPDH activity is required. Conclusions Together, our results suggest a novel mechanism whereby cytoophidium assembly upregulates IMPDH activity and mediates guanine nucleotide homeostasis.

中文翻译：

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IMP/GTP 平衡调节 cytoophidium 组装和 IMPDH 活性。

背景 肌苷一磷酸脱氢酶 (IMPDH) 是 GTP 从头生物合成中的限速酶，在细胞代谢和增殖中起重要作用。已经证明 IMPDH 可以在各种条件下在哺乳动物细胞中聚集成宏观结构，称为细胞毒。然而，细胞毒的调节和功能仍然难以捉摸。结果 在这项研究中，我们报告 IMPDH 的自发丝状化与快速细胞增殖相关。细胞内 IMP 积累促进了 cytoophidium 组装，而升高的 GTP 水平引发了聚集体的解离。通过使用 IMPDH2 CBS 结构域突变细胞模型，这些模型无法形成胞浆，我们已经确定，在需要更高 IMPDH 活性的情况下，细胞毒对于维持 GTP 池和正常细胞增殖至关重要。结论 总之，我们的结果表明了一种新的机制，即 cytoophidium 组装上调 IMPDH 活性并介导鸟嘌呤核苷酸稳态。