The FAD- and O2-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum

Benjamin P. Tu, Jonathan S. Weissman

Research output: Contribution to journalArticlepeer-review

327 Scopus citations

Abstract

The endoplasmic reticulum (ER) supports disulfide formation through an essential protein relay involving Ero1p and protein disulfide isomerase (PDI). We find that in addition to having a tightly associated flavin adenine dinucleotide (FAD) moiety, yeast Ero1p is highly responsive to small changes in physiological levels of free FAD. This sensitivity underlies the dependence of oxidative protein folding on cellular FAD levels. FAD is synthesized in the cytosol but can readily enter the ER lumen and promote Ero1p-catalyzed oxidation. Ero1p then uses molecular oxygen as its preferred terminal electron acceptor. Thus Ero1p directly couples disulfide formation to the consumption of molecular oxygen, but its activity is modulated by free lumenal FAD levels, potentially linking disulfide formation to a cell's nutritional or metabolic status.

Original languageEnglish (US)
Pages (from-to)983-994
Number of pages12
JournalMolecular cell
Volume10
Issue number5
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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