Some aquaporins (AQPs) can transport H₂O₂ across membranes, allowing redox signals to proceed in and between cells. Unlike other peroxiporins, human AQP11 is an endoplasmic reticulum (ER)-resident that can conduit H₂O₂ to the cytosol. Here, we show that silencing Ero1α, an ER flavoenzyme that generates abundant H₂O₂ during oxidative folding, causes a paradoxical increase in luminal H₂O₂ levels. The simultaneous AQP11 downregulation prevents this increase, implying that H₂O₂ reaches the ER from an external source(s). Pharmacological inhibition of the electron transport chain reveals that Ero1α downregulation activates superoxide production by complex III. In the intermembrane space, superoxide dismutase 1 generates H₂O₂ that enters the ER channeled by AQP11. Meanwhile, the number of ER-mitochondria contact sites increases as well, irrespective of AQP11 expression. Taken together, our findings identify a novel interorganellar redox response that is activated upon Ero1α downregulation and transfers H₂O₂ from mitochondria to the ER via AQP11.

一些水通道蛋白 (AQP) 可以跨膜运输 H ₂ O _{2 ，​​从而允许氧化还原信号在细胞内和细胞之间进行。}与其他过氧孔蛋白不同，人 AQP11 是一种内质网 (ER) 驻留物，可以将 H ₂ O ₂引导至细胞质。在这里，我们发现沉默 Ero1α（一种在氧化折叠过程中产生大量 H ₂ O _{2 的内质网黄素酶）会导致管腔 H 2} O ₂水平的反常增加。同时 AQP11 下调阻止了这种增加，这意味着 H ₂ O ₂从外部来源到达 ER。电子传递链的药理学抑制表明 Ero1α 下调可激活复合物 III 产生超氧化物。在膜间空间中，超氧化物歧化酶 1 产生 H ₂ O ₂，通过 AQP11 进入内质网。同时，无论 AQP11 表达如何，ER-线粒体接触位点的数量也会增加。总而言之，我们的研究结果确定了一种新型细胞器间氧化还原反应，该反应在 Ero1α 下调时被激活，并通过 AQP11 将 H ₂ O ₂从线粒体转移到内质网。