Rockefeller University team identifies SLC33A1 as key ER glutathione transporter
Updated
Updated · SciTechDaily · May 1
Rockefeller University team identifies SLC33A1 as key ER glutathione transporter
7 articles · Updated · SciTechDaily · May 1
Published in Nature Cell Biology, the study found SLC33A1 exports oxidized glutathione to maintain the endoplasmic reticulum conditions needed for correct protein folding.
Researchers said disrupting this balance impairs a protein quality-control step, causing misfolded proteins to accumulate in the ER and potentially trigger cell stress and death.
The findings may clarify Huppke-Brindle syndrome biology and suggest therapeutic strategies for neurodevelopmental disorders and KEAP1-mutant lung cancers that depend on high glutathione synthesis.
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SLC33A1 Identified as the Essential ER Transporter for Oxidized Glutathione Export and Redox Homeostasis
Overview
In 2026, the development of a rapid ER immunoprecipitation technique led to the discovery of SLC33A1 as the key transporter exporting oxidized glutathione (GSSG) from the endoplasmic reticulum (ER). Loss or mutation of SLC33A1 causes GSSG to accumulate, creating a hyperoxidizing environment that oxidizes critical protein disulfide isomerases, disrupting protein folding and leading to misfolded protein buildup. This imbalance underlies severe diseases like Huppke-Brendel syndrome, causing developmental defects, and creates a vulnerability in KEAP1-mutant lung cancers, where sustained stress triggers cancer cell death. These insights reveal SLC33A1 as central to ER redox balance and a promising target for therapeutic intervention.