PXD074465

PXD074465 is an original dataset announced via ProteomeXchange.

Title	SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis
Description	The endoplasmic reticulum (ER) requires an oxidative environment to support the efficient maturation of secretory and membrane proteins. This is in part established by glutathione, a redox-active metabolite present in reduced (GSH) and oxidized (GSSG) forms. The ER maintains a higher GSSG:GSH ratio than the cytosol; however, the mechanisms controlling ER redox balance remain poorly understood. To address this, we developed a method for the rapid immunopurification of the ER, enabling comprehensive profiling of its proteome and metabolome. Combining this approach with CRISPR screening, we identified SLC33A1 as the major ER GSSG exporter in mammalian cells. Loss of SLC33A1 leads to GSSG accumulation in the ER and a liposome-based assay demonstrates that SLC33A1 directly transports GSSG. Cryo-EM structures and molecular dynamics simulations reveal how SLC33A1 binds GSSG and identify residues critical for its transport. Finally, an imbalance in GSSG:GSH ratio induces ER stress and dependency on the ER-associated degradation (ERAD) pathway, driven by a shift in protein disulfide isomerases (PDIs) toward their oxidized forms. Altogether, our work establishes SLC33A1-mediated GSSG export as a key mechanism for ER redox homeostasis and protein maturation.
HostingRepository	PRIDE
AnnounceDate	2026-02-19
AnnouncementXML	Submission_2026-02-19_06:21:21.203.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Henry Sanford
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-13 16:56:55	ID requested
⏵ 1	2026-02-19 06:21:21	announced

10.64898/2026.02.01.703113;

submitter keyword: TMT, Mouse,LC-MSMS

Ekaterina V. Vinogradova
contact affiliation	Laboratory of Chemical Immunology and Proteomics, Rockefeller University
contact email	vinograd@rockefeller.edu
lab head
Henry Sanford
contact affiliation	Rockefeller University
contact email	hsanford@rockefeller.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD074465
     1. Label: PRIDE project
     2. Name: SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis