Glutathione balance in the ER, controlled by SLC33A1, is essential for proper protein folding and disease prevention.

Sialic acid O-acetylation occurs in the Golgi apparatus and is catalyzed by CASD1, a multi-pass transmembrane protein. Here, the authors reveal that SLC33A1 delivers acetyl-CoA to the luminal catalytic domain of CASD1, while a catalytic transmembrane tunnel enables SLC33A1-independent O-acetylation.

Read the full paper: SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis

Read the full paper: Pharmacological Inhibition of SLC33A1 Promotes Endoplasmic Reticulum Hyperoxidation and Induces Adaptive IRE1/XBP1s Signaling

How does the ER prevent misfolded proteins? Researchers identify the SLC33A1 transporter as a critical glutathione regulator for protein quality control.

How does the ER prevent misfolded proteins? Researchers identify the SLC33A1 transporter as a critical glutathione regulator for protein quality control.

a, Schematic of the domain structure of the ER transmembrane proteins EMC3, OST4 and SEC63 fused to mScarlet and 3×HA tag. b, Immunoblot analysis of whole-cell lysates (5 µg) and ER-IP lysates (5 µg) with the indicated compartment-specific antibodies. Lysates were derived from flow cytometry sorted HEK293T cells expressing EMC3–mScarlet–3×HA (EMC3-tag), OST4-mScarlet–3×HA (OST4-tag) or SEC63-mScarlet–3×HA (SEC63-tag). E, EMC3-tag; O-L, low expression of OST4-tag; O-M, medium expression of OST4-tag; S-L, low expression of SEC63-tag; S-M, medium expression of SEC63-tag. Immunoblots are representative of three independent experiments with similar results. c, Immunoblot analysis of indicated proteins from HEK293T cells or HEK293T cells expressing control-tag or ER-tag. Immunoblots are representative of three independent experiments with similar results. d, PCA plot of whole cell, ER-IP and control-IP proteomic data from HEK293T cells expressing control-tag or ER-tag. Statistical significance was assessed using a two-sided t-test with permutation-based false discovery rate (FDR) correction (1%). n = 3 biological replicates. e, Bar graph showing fractions of proteins in ER-IP, whole cell and control-IP samples from HEK293T expressing ER-tag or control-tag. Others include proteins except ribosomal and ER proteins. n = 3 biological replicates. f, Volcano plot showing relative fold change (log2) in IP protein abundance versus −log10(adjusted...

Glutathione balance in the ER, controlled by SLC33A1, is essential for proper protein folding and disease prevention. Glutathione is one of the cell’s most versatile defenders, an antioxidant that neutralizes harmful molecules, repairs damage, and helps keep essential systems running smoothly. But scientists are discovering that its role is far more complex and consequential than [...]

In the past several years, Rockefeller University's Kivanç Birsoy and his team in the Laboratory of Metabolic Regulation and Genetics have revealed remarkable details about the antioxidant glutathione, which plays many essential roles in the body, from clearing free radicals to repairing cellular damage.