Show simple item record Lizák, Beáta Birk, Julia Zana, Melinda Kosztyi, Gergely Kratschmar, Denise V Odermatt, Alex Zimmermann, Richard Geiszt, Miklós Appenzeller-Herzog, Christian Bánhegyi, Gábor 2020-09-10T07:03:31Z 2020-09-10T07:03:31Z 2020
dc.identifier.citation journalVolume=18;journalIssueNumber=1;pagination=19, pages: 16;journalTitle=BMC BIOLOGY;journalAbbreviatedTitle=BMC BIOL;
dc.identifier.uri doi:10.1186/s12915-020-0749-y
dc.description.abstract The lumen of the endoplasmic reticulum (ER) acts as a cellular Ca2+ store and a site for oxidative protein folding, which is controlled by the reduced glutathione (GSH) and glutathione-disulfide (GSSG) redox pair. Although depletion of luminal Ca2+ from the ER provokes a rapid and reversible shift towards a more reducing poise in the ER, the underlying molecular basis remains unclear.We found that Ca2+ mobilization-dependent ER luminal reduction was sensitive to inhibition of GSH synthesis or dilution of cytosolic GSH by selective permeabilization of the plasma membrane. A glutathione-centered mechanism was further indicated by increased ER luminal glutathione levels in response to Ca2+ efflux. Inducible reduction of the ER lumen by GSH flux was independent of the Ca2+-binding chaperone calreticulin, which has previously been implicated in this process. However, opening the translocon channel by puromycin or addition of cyclosporine A mimicked the GSH-related effect of Ca2+ mobilization. While the action of puromycin was ascribable to Ca2+ leakage from the ER, the mechanism of cyclosporine A-induced GSH flux was independent of calcineurin and cyclophilins A and B and remained unclear.Our data strongly suggest that ER influx of cytosolic GSH, rather than inhibition of local oxidoreductases, is responsible for the reductive shift upon Ca2+ mobilization. We postulate the existence of a Ca2+- and cyclosporine A-sensitive GSH transporter in the ER membrane. These findings have important implications for ER redox homeostasis under normal physiology and ER stress.
dc.relation.ispartof urn:issn:1741-7007
dc.title Ca2+ mobilization-dependent reduction of the endoplasmic reticulum lumen is due to influx of cytosolic glutathione
dc.type Journal Article 2020-03-09T11:47:33Z
dc.language.rfc3066 en
dc.rights.holder NULL
dc.identifier.mtmt 31199952
dc.identifier.pubmed 32101139
dc.contributor.department SE/AOK/I/Élettani Intézet
dc.contributor.department SE/AOK/I/Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézet
dc.contributor.institution Semmelweis Egyetem

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