Disulphide production by Ero1a-PDI relay is rapid and effectively regulated
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Disulphide production by Ero1a-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. 3318-29.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Disulphide production by Ero1a-PDI relay is rapid and effectively regulated
AU - Appenzeller-Herzog, Christian
AU - Riemer, Jan
AU - Zito, Ester
AU - Chin, King-Tung
AU - Ron, David
AU - Spiess, Martin
AU - Ellgaard, Lars
PY - 2010/10/6
Y1 - 2010/10/6
N2 - 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 Ero1a 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 Ero1a, 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.
AB - 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 Ero1a 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 Ero1a, 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.
KW - Faculty of Science
KW - disulphide-bond formation, endoplasmic reticulum, Ero1, glutathione, protein disulphide isomerase
U2 - 10.1038/emboj.2010.203
DO - 10.1038/emboj.2010.203
M3 - Journal article
C2 - 20802462
VL - 29
SP - 3318
EP - 3329
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 19
ER -
ID: 32202013