The reversal of thiol oxidation in proteins within the endoplasmic reticulum (ER) is crucial for protein folding, degradation, chaperone function, and the ER stress response. Our understanding of this process is generally poor but progress has been made. Enzymes performing the initial reduction of client proteins, as well as the ultimate electron donor in the pathway, have been identified. Most recently, a role for the cytosol in ER protein reduction has been revealed. Nevertheless, how reducing equivalents are transferred from the cytosol to the ER lumen remains an open question. We review here why proteins are reduced in the ER, discuss recent data on catalysis of steps in the pathway, and consider the implications for redox homeostasis within the early secretory pathway.

内质网 (ER) 内蛋白质硫醇氧化的逆转对于蛋白质折叠、降解、伴侣功能和 ER 应激反应至关重要。我们对这一过程的理解普遍较差，但已经取得了进展。已经鉴定出执行客户蛋白初始还原的酶以及途径中的最终电子供体。最近，胞质溶胶在 ER 蛋白减少中的作用已被揭示。然而，还原当量如何从细胞质转移到内质网腔仍然是一个悬而未决的问题。我们在这里回顾为什么蛋白质在内质网中减少，讨论有关该途径步骤催化的最新数据，并考虑对早期分泌途径中氧化还原稳态的影响。