Thiol-based redox switches evolved as efficient post-translational regulatory mechanisms that enable individual proteins to rapidly respond to sudden environmental changes. While some protein functions need to be switched off to save resources and avoid potentially error-prone processes, protective functions become essential and need to be switched on. In this review, we focus on thiol-based activation mechanisms of stress-sensing chaperones. Upon stress exposure, these chaperones convert into high affinity binding platforms for unfolding proteins and protect cells against the accumulation of potentially toxic protein aggregates. Their chaperone activity is independent of ATP, a feature that becomes especially important under oxidative stress conditions, where cellular ATP levels drop and canonical ATP-dependent chaperones no longer operate. Vice versa, reductive inactivation and substrate release require the restoration of ATP levels, which ensures refolding of client proteins by ATP-dependent foldases. We will give an overview over the different strategies that cells evolved to rapidly increase the pool of ATP-independent chaperones upon oxidative stress and provide mechanistic insights into how stress conditions are used to convert abundant cellular proteins into ATP-independent holding chaperones.

中文翻译：

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基于硫醇的压力感应伴侣转换机制

基于硫醇的氧化还原开关进化为有效的翻译后调节机制，使单个蛋白质能够快速响应突然的环境变化。虽然需要关闭一些蛋白质功能以节省资源并避免潜在的容易出错的过程，但保护功能变得必不可少并且需要开启。在这篇综述中，我们关注基于硫醇的压力感应伴侣激活机制。在压力暴露时，这些分子伴侣转化为高亲和力结合平台，用于展开蛋白质并保护细胞免受潜在有毒蛋白质聚集体的积累。它们的分子伴侣活性与 ATP 无关，这一特征在氧化应激条件下变得尤为重要，此时细胞 ATP 水平下降，规范的 ATP 依赖性分子伴侣不再起作用。反之亦然，还原性灭活和底物释放需要 ATP 水平的恢复，这确保了 ATP 依赖性折叠酶对客户蛋白质的重新折叠。我们将概述细胞进化以在氧化应激下迅速增加 ATP 非依赖性分子伴侣池的不同策略，并提供有关如何利用应激条件将丰富的细胞蛋白质转化为 ATP 非依赖性保持分子的机制见解。