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PMID: 14757749 Published · ppublish English Journal Article Review

Oxidative protein folding in eukaryotes: mechanisms and consequences.

The Journal of cell biology ·Vol. 164 ·No. 3 ·2004-02-02 ·Pages 341-6

Tu BP, Weissman JS

Abstract

The endoplasmic reticulum (ER) provides an environment that is highly optimized for oxidative protein folding. Rather than relying on small molecule oxidants like glutathione, it is now clear that disulfide formation is driven by a protein relay involving Ero1, a novel conserved FAD-dependent enzyme, and protein disulfide isomerase (PDI); Ero1 is oxidized by molecular oxygen and in turn acts as a specific oxidant of PDI, which then directly oxidizes disulfide bonds in folding proteins. While providing a robust driving force for disulfide formation, the use of molecular oxygen as the terminal electron acceptor can lead to oxidative stress through the production of reactive oxygen species and oxidized glutathione. How Ero1p distinguishes between the many different PDI-related proteins and how the cell minimizes the effects of oxidative damage from Ero1 remain important open questions.

MeSH Terms
Animals Endoplasmic Reticulum/metabolism Eukaryotic Cells/physiology Glycoproteins/metabolism Humans Membrane Glycoproteins Oxidation-Reduction Oxidoreductases Protein Disulfide-Isomerases/metabolism Protein Folding
Chemicals
Glycoproteins Membrane Glycoproteins ERO1A protein, human Ero1l protein, mouse Oxidoreductases Protein Disulfide-Isomerases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tu Benjamin P
Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94143, USA.
Weissman Jonathan S
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200311055
Published
2004-02-02
Pages
341-6
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172237
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200311055 PMC Full Text View journal details
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