In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport. Increased ER glutathione import triggers H₂O₂-dependent Bip oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction, and cytosolic glutathione levels increase. Thus, the ER redox poise is tuned by reciprocal control of glutathione import and Ero1 activation. The ER protein-conducting channel is permeable to small molecules, provided the driving force of a concentration gradient.

在内质网（ER）中，Ero1催化二硫键的形成并促进谷胱甘肽（GSH）氧化为GSSG。由于不能降低ER中的GSSG，因此维持ER谷胱甘肽氧化还原状态和水平很可能取决于ER谷胱甘肽的进口和GSSG的出口。我们使用定量的GSH和GSSG生物传感器来监测谷胱甘肽导入酵母细胞内质网中。我们发现，谷胱甘肽通过促进通过Sec61蛋白传导通道的扩散而进入内质网，而氧化的Bip（Kar2）抑制转运。ER谷胱甘肽的进口增加触发H ₂ O ₂Ero1还原性激活可抑制依赖的Bip氧化，从而抑制谷胱甘肽在负调控回路中的导入。在内质网应激期间，转运被UPR依赖性的Ero1诱导激活，胞质谷胱甘肽水平增加。因此，通过相互控制谷胱甘肽的导入和Ero1的激活来调节ER的氧化还原平衡。ER蛋白传导通道可渗透小分子，只要浓度梯度的驱动力即可。