Redox controls UPR to control redox
Redox controls UPR to control redox
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DOI：
10.1242/jcs.153643
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发表时间：
2014-09-01
影响因子：
4
通讯作者：
Appenzeller-Herzog, Christian
中科院分区：
文献类型：
--
作者：
Eletto, Davide;Chevet, Eric;Appenzeller-Herzog, Christian
在许多生理环境中，细胞内还原氧化（氧化还原）条件和未折叠蛋白反应（UPR）对于控制细胞的生命和死亡决策非常重要。 UPR 是由内质网 (ER) 稳态破坏（也称为 ER 应激）引发的。根据破坏的持续时间和严重程度，这会导致细胞适应或死亡。在本评论中，我们回顾了 UPR 的还原和氧化激活机制，其中包括专用蛋白质二硫键异构酶与 ER 应激传感器的直接相互作用、蛋白质 S-亚硝基化和活性氧促进的 ER Ca2+ 流出。此外，我们讨论了细胞氧化剂和抗氧化能力如何在 UPR 信号下游被广泛重塑。除了 NADPH 氧化酶、丝裂原激活蛋白激酶和转录抗氧化反应的激活之外，这种重塑主要依赖于 ER 线粒体串扰。因此，特定的氧化还原线索既可以作为内质网应激的触发因素，也可以作为内质网应激的效应因素，从而实现放大循环。我们认为基于氧化还原的放大环路对于从适应性 UPR 到致命性 UPR 的转变至关重要。
In many physiological contexts, intracellular reduction-oxidation (redox) conditions and the unfolded protein response (UPR) are important for the control of cell life and death decisions. UPR is triggered by the disruption of endoplasmic reticulum (ER) homeostasis, also known as ER stress. Depending on the duration and severity of the disruption, this leads to cell adaptation or demise. In this Commentary, we review reductive and oxidative activation mechanisms of the UPR, which include direct interactions of dedicated protein disulfide isomerases with ER stress sensors, protein S-nitrosylation and ER Ca2+ efflux that is promoted by reactive oxygen species. Furthermore, we discuss how cellular oxidant and antioxidant capacities are extensively remodeled downstream of UPR signals. Aside from activation of NADPH oxidases, mitogen-activated protein kinases and transcriptional antioxidant responses, such remodeling prominently relies on ER-mitochondrial crosstalk. Specific redox cues therefore operate both as triggers and effectors of ER stress, thus enabling amplification loops. We propose that redox-based amplification loops critically contribute to the switch from adaptive to fatal UPR.