Disulphide production by Ero1α-PDI relay is rapid and effectively regulated

Christian Appenzeller-Herzog, Jan Riemer, Ester Zito, King Tung Chin, David Ron, Martin Spiess, Lars Ellgaard

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The molecular networks that control endoplasmic reticulum (ER) redox conditions in mammalian cells are incompletely understood. Here, we show that after reductive challenge the ER steady-state disulphide content is restored on a time scale of seconds. Both the oxidase Ero1α and the oxidoreductase protein disulphide isomerase (PDI) strongly contribute to the rapid recovery kinetics, but experiments in ERO1-deficient cells indicate the existence of parallel pathways for disulphide generation. We find PDI to be the main substrate of Ero1α, and mixed-disulphide complexes of Ero1 primarily form with PDI, to a lesser extent with the PDI-family members ERp57 and ERp72, but are not detectable with another homologue TMX3. We also show for the first time that the oxidation level of PDIs and glutathione is precisely regulated. Apparently, this is achieved neither through ER import of thiols nor by transport of disulphides to the Golgi apparatus. Instead, our data suggest that a dynamic equilibrium between Ero1-and glutathione disulphide-mediated oxidation of PDIs constitutes an important element of ER redox homeostasis.

Original languageEnglish
Pages (from-to)3318-3329
Number of pages12
JournalEMBO Journal
Volume29
Issue number19
DOIs
Publication statusPublished - Oct 6 2010

Fingerprint

Protein Disulfide-Isomerases
Endoplasmic Reticulum
Disulfides
Oxidation-Reduction
Oxidoreductases
Oxidation
Glutathione Disulfide
Golgi Apparatus
Sulfhydryl Compounds
Glutathione
Homeostasis
Cells
Recovery
Kinetics
Substrates
Experiments

Keywords

  • disulphide-bond formation
  • endoplasmic reticulum
  • Ero1
  • glutathione
  • protein disulphide isomerase

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Medicine(all)

Cite this

Appenzeller-Herzog, C., Riemer, J., Zito, E., Chin, K. T., Ron, D., Spiess, M., & Ellgaard, L. (2010). Disulphide production by Ero1α-PDI relay is rapid and effectively regulated. EMBO Journal, 29(19), 3318-3329. https://doi.org/10.1038/emboj.2010.203

Disulphide production by Ero1α-PDI relay is rapid and effectively regulated. / Appenzeller-Herzog, Christian; Riemer, Jan; Zito, Ester; Chin, King Tung; Ron, David; Spiess, Martin; Ellgaard, Lars.

In: EMBO Journal, Vol. 29, No. 19, 06.10.2010, p. 3318-3329.

Research output: Contribution to journalArticle

Appenzeller-Herzog, C, Riemer, J, Zito, E, Chin, KT, Ron, D, Spiess, M & Ellgaard, L 2010, 'Disulphide production by Ero1α-PDI relay is rapid and effectively regulated', EMBO Journal, vol. 29, no. 19, pp. 3318-3329. https://doi.org/10.1038/emboj.2010.203
Appenzeller-Herzog C, Riemer J, Zito E, Chin KT, Ron D, Spiess M et al. Disulphide production by Ero1α-PDI relay is rapid and effectively regulated. EMBO Journal. 2010 Oct 6;29(19):3318-3329. https://doi.org/10.1038/emboj.2010.203
Appenzeller-Herzog, Christian ; Riemer, Jan ; Zito, Ester ; Chin, King Tung ; Ron, David ; Spiess, Martin ; Ellgaard, Lars. / Disulphide production by Ero1α-PDI relay is rapid and effectively regulated. In: EMBO Journal. 2010 ; Vol. 29, No. 19. pp. 3318-3329.
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