State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.
Research Unit of Mitochondria in Brain Diseases, Chinese Academy of Medical Sciences, PKU-Nanjing Institute of Translational Medicine, Nanjing, Jiangsu, China.
Cell Res. 2021 Jun;31(6):703-712. doi: 10.1038/s41422-020-00431-3. Epub 2020 Nov 6.
Intracellular pH (pH) homeostasis is crucial for cellular functions and signal transduction across all kingdoms of life. In particular, bacterial pH homeostasis is important for physiology, ecology, and pathogenesis. Here we report an exquisite bacterial acid-resistance (AR) mechanism in which proton leak elicits a pre-emptive AR response. A single bacterial cell undergoes quantal electrochemical excitation, termed "BacFlash", which consists of membrane depolarization, transient pH rise, and bursting production of reactive oxygen species. BacFlash ignition is dictated by acid stress in the form of proton leak across the plasma membrane and the rate of BacFlash occurrence is reversely correlated with the pH buffering capacity. Through genome-wide screening, we further identify the ATP synthase F complex subunit a as the putative proton sensor for BacFlash biogenesis. Importantly, persistent BacFlash hyperactivity activates transcription of a panel of key AR genes and predisposes the cells to survive imminent extreme acid stress. These findings demonstrate a prototypical coupling between electrochemical excitation and nucleoid gene expression in prokaryotes.
细胞内 pH（pH 值）稳态对于所有生命领域的细胞功能和信号转导都至关重要。特别是，细菌的 pH 值稳态对于生理学、生态学和发病机制很重要。在这里，我们报告了一种细菌耐酸（AR）的精细机制，其中质子泄漏引发了抢先的 AR 反应。单个细菌细胞经历称为“BacFlash”的量子电化学激发，其由膜去极化、瞬时 pH 值升高和活性氧的爆发性产生组成。BacFlash 的点火取决于质子通过质膜泄漏的酸胁迫形式，并且 BacFlash 发生的速率与 pH 值缓冲能力呈负相关。通过全基因组筛选，我们进一步确定 ATP 合酶 F 复合物亚基 a 作为 BacFlash 生物发生的假定质子传感器。重要的是，持续的 BacFlash 过度活跃会激活一组关键的 AR 基因的转录，并使细胞更容易在即将到来的极端酸胁迫下存活。这些发现表明了电化学激发和原核生物核基因表达之间的典型耦合。
