Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of viability and stress resistance.
Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of viability and stress resistance.
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DOI：
10.1016/j.molcel.2012.08.009
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发表时间：
2012-10-26
期刊：
影响因子：
16
通讯作者：
Wang, Jue D.
中科院分区：
文献类型：
--
作者：
Kriel, Allison;Bittner, Alycia N.;Kim, Sok Ho;Liu, Kuanqing;Tehranchi, Ashley K.;Zou, Winnie Y.;Rendon, Samantha;Chen, Rui;Tu, Benjamin P.;Wang, Jue D.
细胞不断调整其代谢以应对环境条件，但对生存的主要机制仍知之甚少。我们发现了一个转录后机制，整合饥饿反应与GTP稳态，使生存，制定的核苷酸（p）ppGpp，细菌应激反应和持久性的关键球员。我们发现，（p）ppGpp激活饥饿时的全球代谢变化，允许通过调节GTP生存。结合代谢组学和生物化学的演示，我们发现（p）ppGpp直接抑制多种GTP生物合成酶的活性。这种抑制作用导致枯草芽孢杆菌中的GTP调节稳健而快速，我们证明这对于将GTP水平维持在支持即使在没有饥饿的情况下也能生存的范围内是必不可少的。相应地，如果没有（p）ppGpp，则会发生总体GTP失调，揭示了（p）ppGpp的重要管家功能;事实上，（p）ppGpp的丢失会导致GTP升高导致死亡，这是GTP功能障碍的严重和以前未知的后果。
Cells constantly adjust their metabolism in response to environmental conditions, yet major mechanisms underlying survival remain poorly understood. We discover a post-transcriptional mechanism that integrates starvation response with GTP homeostasis to allow survival, enacted by the nucleotide (p)ppGpp, a key player in bacterial stress response and persistence. We reveal that (p)ppGpp activates global metabolic changes upon starvation, allowing survival by regulating GTP. Combining metabolomics with biochemical demonstrations, we find that (p)ppGpp directly inhibits the activities of multiple GTP biosynthesis enzymes. This inhibition results in robust and rapid GTP regulation in Bacillus subtilis, which we demonstrate is essential to maintaining GTP levels within a range that supports viability even in the absence of starvation. Correspondingly, without (p)ppGpp, gross GTP dysregulation occurs, revealing a vital housekeeping function of (p)ppGpp; in fact, loss of (p)ppGpp results in death from rising GTP, a severe and previously unknown consequence of GTP dysfunction.
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DOI：
10.1073/pnas.0606384103
发表时间：
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影响因子：
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作者：
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影响因子：
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