Competition between glutathione and protein thiols for disulphide-bond formation

It has long been assumed that the oxidized form of glutathione, the tripept ide glutamate-cysteine-glycine, is a source of oxidizing equivalents needed for the formation of disulphide bonds in proteins within the endoplasmic r eticulum (ER), although the in vivo function of glutathione in the ER has n ever been studied directly. Here we show that the major pathway for oxidati on in the yeast ER, defined by the protein Ero1, is responsible for the oxi dation of both glutathione and protein thiols. However, mutation and overex pression studies show that glutathione competes with protein thiols for the oxidizing machinery. Thus, contrary to expectation, cellular glutathione c ontributes net reducing equivalents to the ER; these reducing equivalents c an buffer the ER against transient hyperoxidizing conditions.