Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut 06536, USA.
Yale Microbial Sciences Institute, West Haven, Connecticut 06516, USA.
Genes Dev. 2018 Jan 1;32(1):79-92. doi: 10.1101/gad.309245.117. Epub 2018 Feb 1.
Phosphorus is an essential element assimilated largely as orthophosphate (Pi). Cells respond to Pi starvation by importing Pi from their surroundings. We now report that impaired protein synthesis alone triggers a Pi starvation response even when Pi is plentiful in the extracellular milieu. In the bacterium serovar Typhimurium this response entails phosphorylation of the regulatory protein PhoB and transcription of PhoB-dependent Pi transporter genes and is eliminated upon stimulation of adenosine triphosphate (ATP) hydrolysis. When protein synthesis is impaired due to low cytoplasmic magnesium (Mg), triggers the Pi starvation response because ribosomes are destabilized, which reduces ATP consumption and thus free cytoplasmic Pi. This response is transient because low cytoplasmic Mg promotes an uptake in Mg and a decrease in ATP levels, which stabilizes ribosomes, resulting in ATP consumption and Pi increase, thus ending the response. Notably, pharmacological inhibition of protein synthesis also elicited a Pi starvation response in the bacterium and the yeast Our findings identify a regulatory connection between protein synthesis and Pi homeostasis that is widespread in nature.
磷是一种主要以正磷酸盐（Pi）形式被同化的必需元素。细胞通过从周围环境中摄取 Pi 来响应 Pi 饥饿。我们现在报告说，即使细胞外环境中 Pi 丰富，仅蛋白质合成受损也会引发 Pi 饥饿反应。在细菌 血清型 Typhimurium 中，这种反应需要调节蛋白 PhoB 的磷酸化以及 PhoB 依赖性 Pi 转运体基因的转录，并且在刺激三磷酸腺苷 (ATP) 水解时被消除。当由于细胞质镁 (Mg) 水平低而导致蛋白质合成受损时， 会引发 Pi 饥饿反应，因为核糖体不稳定，从而减少 ATP 消耗，从而导致游离细胞质 Pi 减少。这种反应是短暂的，因为细胞质镁水平低会促进镁的摄取和 ATP 水平的降低，从而稳定核糖体，导致 ATP 消耗和 Pi 的增加，从而结束反应。值得注意的是，蛋白质合成的药理学抑制也会在细菌 和酵母 中引发 Pi 饥饿反应。我们的发现确定了蛋白质合成和 Pi 动态平衡之间的一种广泛存在于自然界中的调节联系。
