Transient intracellular acidification regulates the core transcriptional heat shock response
Transient intracellular acidification regulates the core transcriptional heat shock response
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DOI：
10.7554/elife.54880
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发表时间：
2020-08-07
期刊：
影响因子：
7.7
通讯作者：
Drummond, D. Allan
中科院分区：
文献类型：
--
作者：
Triandafillou, Catherine G.;Katanski, Christopher D.;Drummond, D. Allan
热休克在真核细胞中诱导受热休克因子 1 (Hsf1) 调节的保守转录程序。这种热休克反应的激活是由热诱导的新合成多肽错误折叠触发的，因此被认为取决于正在进行的蛋白质合成。在这里，我们利用芽殖酵母酿酒酵母发现，只要细胞经历胞质酸化，当蛋白质合成受到抑制时，Hsf1就可以被强烈激活。人们早就知道热休克会导致短暂的细胞内酸化，但其原因尚不清楚，它与真核生物的应激抵抗力增强有关。我们证明，在翻译受抑制的细胞中，酸化是诱导热休克反应所必需的，并且特别影响 Hsf1 的激活。生理热引发的酸化还可以增加群体适应性并促进热休克后细胞周期的重新进入。我们的结果揭示了经过充分研究的真核热休克反应的先前未知的适应性维度。
Heat shock induces a conserved transcriptional program regulated by heat shock factor 1 (Hsf1) in eukaryotic cells. Activation of this heat shock response is triggered by heat-induced misfolding of newly synthesized polypeptides, and so has been thought to depend on ongoing protein synthesis. Here, using the budding yeast Saccharomyces cerevisiae, we report the discovery that Hsf1 can be robustly activated when protein synthesis is inhibited, so long as cells undergo cytosolic acidification. Heat shock has long been known to cause transient intracellular acidification which, for reasons which have remained unclear, is associated with increased stress resistance in eukaryotes. We demonstrate that acidification is required for heat shock response induction in translationally inhibited cells, and specifically affects Hsf1 activation. Physiological heat-triggered acidification also increases population fitness and promotes cell cycle reentry following heat shock. Our results uncover a previously unknown adaptive dimension of the well-studied eukaryotic heat shock response.