Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia.
Res Microbiol. 2023 Nov-Dec;174(8):104108. doi: 10.1016/j.resmic.2023.104108. Epub 2023 Jul 27.
Metabolic rearrangements that occur during depletion of essential nutrients can lead to accumulation of potentially dangerous metabolites. Here we showed that depletion of phosphate (P), accompanied by a sharp inhibition of growth and respiration, caused a transient excess of intracellular cysteine due to a decrease in the rate of protein synthesis. High cysteine level can be dangerous due to its ability to produce ROS and reduce Fe to Fenton-reactive Fe. To prevent these negative effects, excess cysteine was mainly incorporated into glutathione (GSH), the intracellular level of which increased by 3 times, and was also exported to the medium and partially degraded to form HS with participation of 3-mercaptopyruvate sulfotransferase (3MST). The addition of P to starving cells led to a sharp recovery of respiration and growth, GSH efflux into the medium and K influx into the cells. A pronounced coupling of P, GSH, and K fluxes was shown upon P depletion and addition, which may be necessary to maintain the ionic balance in the cytoplasm. We suggest that processes aimed at restoring cysteine homeostasis may be an integral part of the universal response to stress under different types of stress and for different types of bacteria.
在必需营养素耗尽期间发生的代谢重排可能导致潜在危险代谢物的积累。在这里，我们表明，磷酸盐（P）的耗尽伴随着生长和呼吸的急剧抑制，由于蛋白质合成速率的降低，导致细胞内半胱氨酸的短暂过量。由于其产生 ROS 和将 Fe 还原为 Fenton 反应性 Fe 的能力，高半胱氨酸水平可能是危险的。为了防止这些负面影响，过量的半胱氨酸主要掺入谷胱甘肽（GSH）中，细胞内 GSH 的水平增加了 3 倍，并且还被运出到培养基中，并部分降解形成 HS，参与 3-巯基丙酮酸磺基转移酶（3MST）。向饥饿细胞中添加 P 会导致呼吸和生长的急剧恢复，GSH 向培养基中的流出和 K 向细胞内的流入。在 P 耗尽和添加时显示出 P、GSH 和 K 通量的明显偶联，这可能对于维持细胞质中的离子平衡是必需的。我们认为，旨在恢复半胱氨酸稳态的过程可能是对不同类型的应激和不同类型的细菌的普遍应激反应的一个组成部分。
