Role of PDI in electron transfer in the mammalian endoplasmic reticulum.
Molecular O2 oxidizes reduced proteins in the ER via Ero and PDI, generating hydrogen peroxide (above); hydrogen peroxide can also oxidize reduced proteins via Gpx 7 and/or 8 and PDI (below). The Gpx7/8 pathway provides efficient use of oxidizing equivalents and detoxification of hydrogen peroxide. PDI interacts with both Ero and Gpx7/8 and, in both pathways, it acts on substrate proteins as the immediate oxidant and isomerase. In this representation, electrons flow from right to left, from a reduced protein to a terminal electron acceptor such as O2; alternatively, oxidizing equivalents can be considered to flow from left to right.