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Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of viability and stress resistance.

Abstract：

:Cells constantly adjust their metabolism in response to environmental conditions, yet major mechanisms underlying survival remain poorly understood. We discover a posttranscriptional 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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Kriel A,Bittner AN,Kim SH,Liu K,Tehranchi AK,Zou WY,Rendon S,Chen R,Tu BP,Wang JD

doi

10.1016/j.molcel.2012.08.009

subject

Has Abstract

pub_date

2012-10-26 00:00:00

pages

231-41

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(12)00696-X

journal_volume

48

pub_type

杂志文章

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