Our finding disproves the main finding of Duce et al . (Cell (2010) 142:857-867). Duce et al. used biochemical methods and showed that the E2 domain of APP has ferroxidase activity. They used this conclusion to interpret their molecular biology experiments based on which they suggested APP facilitates export of Fe(II) from ferroportin by oxidizing Fe(II) to Fe(III) and subsequent binding of Fe(III) to transferrin. We show that E2 domain of APP does not have ferroxidase activity. Thus, APP cannot facilitate export of Fe(II). Whether APP can interact with ferroportin, transferrin or other proteins and participate in iron export is not clear based on experiments reported by Duce et al. Such a protein interaction should be studied under appropriate experimental conditions.
