Model of inter- and intramolecular electron transfer cascade among ER oxidoreductases. (A) Proposed model for the synergistic effect. Details are described in the Discussion. ERp57 and P5 could be oxidized in a similar fashion to that of ERp46. (B) The intracellular amounts of several ER oxidoreductases in HEK293T or HeLa cells were roughly estimated by immunoblot analysis using the appropriate antibodies, with parallel loading of recombinant proteins on the same gel. The intracellular amounts of PDI, ERp57, P5, and ERp72 were roughly similar, but those of ERp46 and ERp44 were about one fifth of the former. The amount of Ero1-α was only one tenth that of PDI. Black lines indicate the removal of intervening lanes from some of the gels for presentation purposes. (C) Proposed model for electron transfer cascades among the ER oxidoreductases. Red and purple arrows indicate the directions of electron transport. Broken line or arrows indicate a nonredox-based interaction or presumed electron transport, respectively. The apparent redox equilibrium constants are from Fig. 6 B. The relative intracellular amounts of these oxidoreductases are indicated by the box sizes.