Establishment of a system for monitoring endoplasmic reticulum redox state in mammalian cells

内质网（ER）在新生蛋白质的氧化折叠中起关键作用，因此ER稳态的扰动可能导致蛋白质错误折叠和随后的病理过程。在维持ER稳态的机制中，氧化还原调节是ER应激细胞命运的关键决定因素。在这里，我们报告了一个系统的建立，用于监测ER的氧化还原状态在哺乳动物细胞。新的ER氧化还原传感系统是基于先前描述的酵母中的监测系统开发的。我们的系统可以成功地监测哺乳动物细胞中的动态ER氧化还原状态。使用这个系统，我们发现，ER氧化酶的操纵改变ER氧化还原状态。哺乳动物ER氧化还原传感系统可用于研究ER氧化还原调节机制，并为开发与ER稳态失调相关的人类疾病（包括神经退行性疾病）的新治疗方法提供基础。

The endoplasmic reticulum (ER) performs a critical role in the oxidative folding of nascent proteins such that perturbations to ER homeostasis may lead to protein misfolding and subsequent pathological processes. Among the mechanisms for maintaining ER homeostasis is a redox regulation, which is a critical determinant of the fate of ER stressed cells. Here we report the establishment of a system for monitoring ER redox state in mammalian cells. The new ER redox sensing system was developed based on the previously described monitoring system in yeast. Our system could successfully monitor the dynamic ER redox state in mammalian cells. Using this system, we find that manipulation of ER oxidases changes ER redox state. The mammalian ER redox sensing system could be used to study the mechanisms of ER redox regulation and provide a foundation for an approach to develop novel therapeutic modalities for human diseases related to dysregulated ER homeostasis including neurodegeneration.