Bacterial cell cycle control by citrate synthase independent of enzymatic activity
Bacterial cell cycle control by citrate synthase independent of enzymatic activity
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DOI：
10.7554/elife.52272
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发表时间：
2020-03-09
期刊：
影响因子：
7.7
通讯作者：
Viollier, Patrick H.
中科院分区：
文献类型：
--
作者：
Berge, Matthieu;Pezzatti, Julian;Viollier, Patrick H.
增殖细胞必须协调中心代谢与细胞周期。中枢能量代谢如何调节细菌细胞周期功能尚不清楚。我们的正向遗传选择发现克雷布斯循环酶柠檬酸合酶 (CitA) 作为检查点调节剂控制极化 α-变形菌新月柄杆菌（细胞周期调节和不对称细胞分裂的模型）中的 G(1) -> S 转变。我们发现，CitA 的缺失会促进活性 CtrA 的积累，CtrA 是一种重要的细胞周期转录调节因子，可在 (p)ppGpp 警报素存在的情况下维持细胞处于 G(1) 期。 CitA 的酶活性对于 CtrA 控制来说是可有可无的，功能性柠檬酸合酶旁系同源物不能取代 CitA 来促进 S 期进入。我们的证据表明，CitA 专门用作兼职酶，将中央能量代谢与进入 S 期联系起来。中央代谢酶对 G(1) 相的控制可能是细胞调节的常见机制。
Proliferating cells must coordinate central metabolism with the cell cycle. How central energy metabolism regulates bacterial cell cycle functions is not well understood. Our forward genetic selection unearthed the Krebs cycle enzyme citrate synthase (CitA) as a checkpoint regulator controlling the G(1) -> S transition in the polarized alpha-proteobacterium Caulobacter crescentus, a model for cell cycle regulation and asymmetric cell division. We find that loss of CitA promotes the accumulation of active CtrA, an essential cell cycle transcriptional regulator that maintains cells in G(1)-phase, provided that the (p)ppGpp alarmone is present. The enzymatic activity of CitA is dispensable for CtrA control, and functional citrate synthase paralogs cannot replace CitA in promoting S-phase entry. Our evidence suggests that CitA was appropriated specifically to function as a moonlighting enzyme to link central energy metabolism with S-phase entry. Control of the G(1)-phase by a central metabolic enzyme may be a common mechanism of cellular regulation.