Evidence map›Paper›PMID 41998286›Full record

ArticleNature cell biology2026

SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis.

Shanshan Liu, Mark Gad, Caifan Li, Kevin Cho, Yuyang Liu, Khando Wangdu, Viktor Belay, Alon Millet, Hiroyuki Kojima, Henry Sanford and 7 more

Abstract read
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In one paragraph

Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Shanshan Liu *Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.
Mark Gad *Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.
Caifan LiLaboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0009-0009-5261-8172
Kevin ChoDepartment of Chemistry, Washington University, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-3041-3506
Yuyang LiuLaboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0001-5632-7764
Khando WangduLaboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.
Viktor BelayStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Alon MilletLaboratory of Systems Cancer Biology, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0001-6514-0459
Hiroyuki KojimaLaboratory of Chemical Immunology and Proteomics, The Rockefeller University, New York, NY, USA.
Henry SanfordLaboratory of Chemical Immunology and Proteomics, The Rockefeller University, New York, NY, USA.
Michele WölkCenter of Membrane Biochemistry and Lipid Research, University Hospital and Faculty of Medicine Carl Gustav Carus of Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0000-0001-5558-4582
Linas UrnaviciusLaboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY, USA.
Maria FedorovaCenter of Membrane Biochemistry and Lipid Research, University Hospital and Faculty of Medicine Carl Gustav Carus of Dresden University of Technology, Dresden, Germany.ORCID http://orcid.org/0000-0002-4692-3885
Gary J PattiDepartment of Chemistry, Washington University, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-3748-6193
Ekaterina V VinogradovaLaboratory of Chemical Immunology and Proteomics, The Rockefeller University, New York, NY, USA.
Richard K HiteStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. hiter@mskcc.org.ORCID http://orcid.org/0000-0003-0496-0669
Kıvanç BirsoyLaboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA. kbirsoy@rockefeller.edu.ORCID http://orcid.org/0000-0002-7579-9895

Funding

Molecular mechanisms of protein functionR35GM156616 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Richard Kevin Hite · 2025 to 2026
$1.3M
NIGMS NIH HHS R35 GM156616
6 · The paper itself

Abstract

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 led to GSSG accumulation in the ER and a liposome-based assay demonstrated that SLC33A1 directly transports GSSG. Cryogenic electron microscopy structures and molecular dynamics simulations revealed how SLC33A1 binds GSSG and identified residues critical for its transport. Finally, an imbalance in GSSG:GSH ratio induced ER stress and dependency on the ER-associated degradation pathway, driven by a shift in protein disulfide isomerases towards their oxidized forms. Together, our work establishes SLC33A1-mediated GSSG export as a key mechanism for ER redox homeostasis and protein maturation.

Indexed as

Cation Transport ProteinsEndoplasmic ReticulumGlutathioneGlutathione DisulfideHomeostasisAnimalsHEK293 CellsHumansOxidation-ReductionCation Transport ProteinsGlutathioneGlutathione Disulfide

Identifiers

PMID41998286

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.