Production of H 2O 2 in the endoplasmic reticulum promotes in vivo disulfide bond formation

Éva Margittai, Péter Löw, Ibolya Stiller, Alessandra Greco, Jose Manuel Garcia-Manteiga, Niccolo Pengo, Angelo Benedetti, Roberto Sitia, Gábor Bánhegyi

Research output: Contribution to journalArticlepeer-review


Aims: Oxidative protein folding in the luminal compartment of endoplasmic reticulum (ER) is thought to be accompanied by the generation of H 2O 2, as side-product of disulfide bond formation. We aimed to examine the role of H 2O 2 produced in the lumen, which on one hand can lead to redox imbalance and hence can contribute to ER stress caused by overproduction of secretory proteins; on the other hand, as an excellent electron acceptor, H 2O 2 might serve as an additional pro-oxidant in physiological oxidative folding. Results: Stimulation of H 2O 2 production in the hepatic ER resulted in a decrease in microsomal GSH and protein-thiol contents and in a redox shift of certain luminal oxidoreductases in mice. The oxidative effect, accompanied by moderate signs of ER stress and reversible dilation of ER cisternae, was prevented by concomitant reducing treatment. The imbalance also affected the redox state of pyridine nucleotides in the ER. Antibody producing cells artificially engineered with powerful luminal H 2O 2 eliminating system showed diminished secretion of mature antibody polymers, while incomplete antibody monomers/dimers were accumulated and/or secreted. Innovation: Evidence are provided by using in vivo models that hydrogen peroxide can promote disulfide bond formation in the ER. Conclusion: The results indicate that local H 2O 2 production promotes, while quenching of H 2O 2 impairs disulfide formation. The contribution of H 2O 2 to disulfide bond formation previously observed in vitro can be also shown in cellular and in vivo systems. Antioxid. Redox Signal.

Original languageEnglish
Pages (from-to)1088-1099
Number of pages12
JournalAntioxidants and Redox Signaling
Issue number10
Publication statusPublished - May 15 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry


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