title: Multiple ways to make disulfides.
abstract: Our concept of how disulfides form in proteins entering the secretory pathway has changed dramatically in recent years. The discovery of endoplasmic reticulum (ER) oxidoreductin 1 (ERO1) was followed by the demonstration that this enzyme couples oxygen reduction to de novo formation of disulfides. However, mammals deficient in ERO1 survive and form disulfides, which suggests the presence of alternative pathways. It has recently been shown that peroxiredoxin 4 is involved in peroxide removal and disulfide formation. Other less well-characterized pathways involving quiescin sulfhydryl oxidase, ER-localized protein disulfide isomerase peroxidases and vitamin K epoxide reductase might all contribute to disulfide formation. Here we discuss these various pathways for disulfide formation in the mammalian ER and highlight the central role played by glutathione in regulating this process.
authors.affiliation: Institute of Molecular, Cellular and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. neil.bulleid@glasgow.ac.uk
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Bulleid
authors.forename: Lars
authors.initials: L
authors.lastname: Ellgaard
mesh_terms: D000818:Animals; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008322:Mammals; D008562:Membrane Glycoproteins / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D017510:Protein Folding; D064417:Vitamin K Epoxide Reductases; D015003:Yeasts / Q000378:metabolism
chemical_list: D004220:Disulfides; D008562:Membrane Glycoproteins; D010545:Peroxides; D006861:Hydrogen Peroxide; C405327:ERO1A protein, human; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D054464:Peroxiredoxins; D064417:Vitamin K Epoxide Reductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; D019704:Protein Disulfide-Isomerases; D005978:Glutathione; D003545:Cysteine