What differentiates a stress response from responsiveness in general?
What differentiates a stress response from responsiveness in general?
复制标题
压力反应与一般反应有何不同？
DOI：
10.1016/j.cels.2022.02.002
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发表时间：
2022
期刊：
影响因子：
9.3
通讯作者：
Israni-Winger, Kavita
中科院分区：
文献类型：
--
作者：
Vogel, Christine;Balázsi, Gábor;Löwer, Alexander;Jiang, Caifu;Schmid, Amy K.;Sommer, Morten;Yang, Laurence;Münch, Christian;Wang, Andrew;Israni-Winger, Kavita
没有一个万能的解决方案细胞压力源是丰富多样的，它们可以是急性或慢性，轻度或强烈。因此，应激反应是复杂的，涉及转录、RNA稳定性、翻译、蛋白质周转和相互作用的变化，以及分子的修饰和重新定位。不同的反应类型有其特定的触发器、调节器和动力学，共同的目标是重建细胞健康，因此缺乏一种通用的解决方案是一件好事。首先，压力反应网络，由不同途径的整体及其相互之间的连接组装而成，提供了适应压力源的类型，强度和动态的灵活性。其次，它允许在多个水平上保护细胞，即确保蛋白质的正确丰度和折叠以及遗传物质的保护。第三，重要的是，响应网络提供了鲁棒性：如果一个路径失败，其他路径仍然可以提供保护。健壮性与灵活性和不确定性一样重要，它们深深地交织在一起。研究所面临的挑战是完全接受这种复杂性。例如，除了破译特定途径的细节之外，完全理解复杂性将需要随着时间的推移对多个过程和许多基因进行同时分析，例如，对翻译变化进行分析，以及沿着转录和蛋白质稳定性的变化。这需要接受例外是规则，没有任何单一的途径可以解释一切。最后，它将需要以一种整合多维数据集的方式整合它们之间的生物学关系，以提取新的见解，并将高度整合的压力反应视为一个大于其部分之和的系统。
No one-size-fits-all solution Cellular stressors are abundant and diverse, and they can be acute or chronic and mild or intense. Accordingly, the stress response is complex, involving transcription, RNA stability, translation, protein turnover, and changes in interactions, as well as modifications and re-localization of molecules. Different response types have their specific triggers, regulators, and dynamics, with the common goal of reestablishing cellular health.The resulting lack of a one-size-fits-all solution is a good thing. First, a stress response network, assembled from the entirety of the different pathways and their connections among each other, provides the flexibility to adjust to the type, intensity, and dynamics of the stressor. Second, it allows cellular protection at multiple levels, ie, ensuring the correct abundance and folding of proteins as well as the protection of the genetic material. Third, and importantly, a response network provides robustness: if one pathway fails, other pathways can still provide protection. Robustness is as critical as flexibility and uncertainty, and they are deeply intertwined. The challenge for research is to fully embrace this complexity. For example, in addition to deciphering the details of specific pathways, fully understanding the complexity would require simultaneous analysis of multiple processes over time and for many genes, eg, profiling of translation changes, along with changes in transcript and protein stability. It would require accepting that exceptions are the rule, and that no single pathway will explain everything. And finally, it would require an integration of the resulting multi-dimensional datasets in a way that incorporates the biological relationships between them to extract new insights and to foster a view of the highly integrated stress response as a system that is bigger than the sum of its parts.