Ero1

ERO1 stands for endoplasmic reticulum oxidoreductin 1. It is a thiol oxidase in the lumen of the endoplasmic reticulum and a key driver of oxidative protein folding. ERO1 reoxidizes reduced protein disulfide isomerase (PDI), replenishing PDI's oxidized state that introduces disulfide bonds into nascent polypeptides. The electrons flow from reduced PDI to ERO1, via its FAD cofactor, and finally to molecular oxygen, generating hydrogen peroxide as a byproduct.

In yeast, ERO1 belongs to the core oxidative folding system of the ER. It is a soluble luminal enzyme that functions in concert with PDI family members to reoxidize PDI and sustain disulfide-bond formation in secreted and membrane proteins. In mammals, two conserved homologs, ERO1-Lalpha and ERO1-Lbeta, contribute to the same oxidative folding pathway and can vary in tissue distribution and activity.

Regulation and significance: ERO1 activity is influenced by the ER redox state and cellular stress responses. Increased ERO1 activity can boost oxidative folding capacity but also raise hydrogen peroxide production, linking ERO1 to ER redox homeostasis and oxidative stress. Defects or altered expression of ERO1 family members are associated with impaired secretory protein maturation and may contribute to diseases characterized by ER stress.