Instituto de Agroquímica y Tecnología de los Alimentos, IATA-CSIC, E-46980, Paterna, Valencia, Spain.
Microb Biotechnol. 2018 May;11(3):465-475. doi: 10.1111/1751-7915.13032. Epub 2018 Feb 22.
The toxic effect of ethanol is one of the most important handicaps for many biotechnological applications of yeasts, such as bioethanol production. Elucidation of ethanol stress response will help to improve yeast performance in biotechnological processes. In the yeast Saccharomyces cerevisiae, ethanol stress has been recently described as an activator of the unfolded protein response (UPR), a conserved intracellular signalling pathway that regulates the transcription of ER homoeostasis-related genes. However, the signal and activation mechanism has not yet been unravelled. Here, we studied UPR's activation after ethanol stress and observed the upregulation of the key target genes, like INO1, involved in lipid metabolism. We found that inositol content influenced UPR activation after ethanol stress and we observed significant changes in lipid composition, which correlate with a major membrane fluidity alteration by this amphipathic molecule. Then, we explored the hypothesis that membrane fluidity changes cause UPR activation upon ethanol stress by studying UPR response against fluidification or rigidification agents and by studying a mutant, erg2, with altered membrane fluidity. The results suggest that the membrane fluidification effects of ethanol and other agents are the signal for UPR activation, a mechanism that has been proposed in higher eukaryotes.
乙醇的毒性作用是酵母许多生物技术应用（如生物乙醇生产）的最重要障碍之一。阐明乙醇应激反应将有助于提高酵母在生物技术过程中的性能。在酵母酿酒酵母中，乙醇应激最近被描述为未折叠蛋白反应 (UPR) 的激活剂，UPR 是一种保守的细胞内信号通路，调节内质网稳态相关基因的转录。然而，信号和激活机制尚未被揭示。在这里，我们研究了乙醇胁迫后 UPR 的激活，并观察到参与脂质代谢的关键靶基因，如 INO1 的上调。我们发现肌醇含量影响乙醇胁迫后的 UPR 激活，并且我们观察到脂质组成发生了显著变化，这与这种两亲分子引起的主要膜流动性改变相关。然后，我们通过研究对抗流体化或刚性化剂的 UPR 反应以及通过研究具有改变的膜流动性的突变体 erg2，探索了这样一种假设，即膜流动性变化导致乙醇胁迫时 UPR 的激活。这一机制在高等真核生物中已经被提出。
