In the canonical oxidative folding pathway in the ER, reduced PDIs from nascent chains are oxidized by Ero1alpha. Ero1alpha releases electrons to molecular oxygen through FAD, producing H2O2 (black and blue arrow lines). Most electrons from the pathway of oxidative folding by PDI-Ero1alpha are diverted to the production of H2O2, and some of those electrons are utilized to produce reductive force in ERdj5 (red arrow line). In fact, Ero1alpha specifically binds the active sites of the Trx3 and Trx4 domains in ERdj5. ERdj5 is reduced by only Ero1alpha and inhibits the oxygen consumption of Ero1alpha, which implies that ERdj5 hijacks electrons from the canonical pathway of oxidative folding by PDI-Ero1alpha.
