Laboratoire Matière et Systèmes Complexes, UMR 7057 CNRS & Université Paris Diderot, 10 rue Alice Domon et Léonie Duquet, Paris, France.
Laboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR 5239, Inserm, U1293, Université Claude Bernard Lyon 1, 46 allée d'Italie F-69364, Lyon, France.
Elife. 2024 Apr 3;12:RP88750. doi: 10.7554/eLife.88750.
Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival, and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer, and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. Therefore, glucose availability regulates yeast responses to dynamic osmotic stress, showcasing the key role of metabolic fluctuations in cellular responses to dynamic stress. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions.
生物生存的自然环境通常是动态的、多因素的，多个参数随时间波动。为了更好地理解细胞如何对动态相互作用的因素做出反应，我们使用微流控和延时显微镜技术，量化了渗透压胁迫和葡萄糖剥夺这两种因素的双重波动对酵母细胞的影响。惊人的是，我们观察到细胞增殖、存活和信号传递取决于这两种周期性胁迫的相位关系。当高渗透压胁迫和葡萄糖剥夺的波动同相时，细胞分裂更快，存活时间更长，转录反应降低，而当两种胁迫交替出现时则不是这样。因此，葡萄糖的可用性调节了酵母对动态渗透压胁迫的反应，展示了代谢波动在细胞对动态胁迫反应中的关键作用。我们还发现，渗透压胁迫反应受损的突变体比野生型细胞更能适应交替胁迫，表明适应持续胁迫因素的遗传机制在动态相互作用条件下可能是有害的。
