Oxidative protein folding fidelity and redoxtasis in the endoplasmic reticulum, Trends Biochem Sci, 20 Jul 2022
Trends in Biochemical Sciences, 20 July, 2022, DOI：https://doi.org/10.1016/j.tibs.2022.06.011
Oxidative protein folding fidelity and redoxtasis in the endoplasmic reticulum
Lei Wang, Chih-chen Wang
In eukaryotic cells, oxidative protein folding occurs in the lumen of the endoplasmic reticulum (ER), catalyzed by ER sulfhydryl oxidase 1 (Ero1) and protein disulfide isomerase (PDI). The efficiency and fidelity of oxidative protein folding are vital for the function of secretory cells. Here, we summarize oxidative protein folding in yeast, plants, and mammals, and discuss how the conformation and activity of human Ero1-PDI machinery is regulated through various post-translational modifications (PTMs). We propose that oxidative protein folding fidelity and ER redox homeostasis are maintained by both the precise control of Ero1 oxidase activity and the division of labor between PDI family members. We also discuss how deregulated Ero1-PDI functions contribute to human diseases and can be leveraged for therapeutic interventions.