Intracellular catalysis of disulfide bond formation by the human sulfydryl oxidase, QSOX1

The discovery that the flavoprotein oxidase, Erv2p, provides oxidising potential for disulphide bond formation in yeast, has led to investigations into the roles of the mammalian homologues of this protein. Mammalian homologues of Erv2p include sulphydryl oxidases from human lung fibroblasts, guinea-pig endometrial cells and rat seminal vesicles. Here we show that when expressed in mammalian cells the longer version of human QSOX1 protein (hQSOX1a) is a transmembrane protein localised primarily to the Golgi apparatus. We also present the first evidence showing that hQSOX1a can act as an oxidase in vivo. Overexpression of hQSOX1a suppresses the lethality of a complete deletion of ERO1 in yeast and restores disulphide bond formation as assayed by the folding of the secretory protein carboxypeptidase Y.