ER-GUARD: an evolutionarily conserved antioxidant defense system at ER membranes.

ABSTRACT: Oxidative protein folding in the endoplasmic reticulum (ER) is essential for all eukaryotic cells yet generates hydrogen peroxide (H₂O₂), a reactive oxygen species (ROS). The ER-transmembrane protein that provides reducing equivalents to ER and guards the cytosol for antioxidant defense remains unidentified. Here we combine AlphaFold2-based and functional reporter screens in C. elegans to identify a previously uncharacterized and evolutionarily conserved protein ERGU-1 that fulfills these roles. Deleting C. elegans ERGU-1 causes excessive H₂O₂ and transcriptional gene up-regulation through SKN-1, homolog of mammalian antioxidant master regulator NRF2. ERGU-1 deficiency also impairs organismal reproduction and behaviors. Both C. e

SUBMITTER: Ji Z 

PROVIDER: S-EPMC11212984 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature