{
  "abstract": "SUMMARY: Oxidative protein folding in the endoplasmic reticulum (ER) is essential for eukaryotic cells yet generates hydrogen peroxide (H2O2), a reactive oxygen species. The ER-transmembrane protein that supports ER proteostasis and guards the cytosol for antioxidant defense remains unidentified. Here, we combine AlphaFold2 and functional screens in C. elegans to discover a previously uncharacterized and evolutionarily conserved protein ERGU-1 that fulfills these roles. Deleting ERGU-1 upregulates H2O2 and NRF2/SKN-1-dependent gene expression. ERGU-1 deficiency also impairs organismal reproduction and behavioral responses to H2O2. Both C. elegans ERGU-1 and human homolog TMEM161B localize to ER membranes, forming reticular networks. Human and Drosophila homologs of ERGU-1 rescue C. elegans mutant phenotypes, demonstrating ancient and conserved functions. In addition, purified ERGU-1 and TMEM161B exhibit redox-modulated oligomeric states. Together, our results reveal an ER-membrane-specific machinery, suggesting a conserved mechanism for maintaining ER redox homeostasis and proteostasis in animal cells.",
  "abstract_shown": true,
  "affiliations": [
    "Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA",
    "Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA",
    "School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China",
    "MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China",
    "Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA",
    "Department of Physiology, University of California San Francisco, San Francisco, CA, USA",
    "Innovative Genomics Institute, Berkeley, CA, USA",
    "Lead contact"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhijian Ji"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Henry de Belly"
    },
    {
      "affs": [
        0
      ],
      "name": "Taruna Pandey"
    },
    {
      "affs": [
        0
      ],
      "name": "Bingying Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yao Tang"
    },
    {
      "affs": [
        3
      ],
      "name": "Jingxuan Yao"
    },
    {
      "affs": [
        3
      ],
      "name": "Shiya Xu"
    },
    {
      "affs": [
        4
      ],
      "name": "Kathy Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanchang Bian"
    },
    {
      "affs": [
        2
      ],
      "name": "Shouhong Guang"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhiyong Lou"
    },
    {
      "affs": [
        4
      ],
      "name": "Al Burlingame"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Orion D. Weiner"
    },
    {
      "affs": [
        4
      ],
      "name": "Thomas D. Goddard"
    },
    {
      "affs": [
        0,
        5,
        6,
        7
      ],
      "name": "Dengke K. Ma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/btf3gcf28zkjf.bib",
  "cited_by": 0,
  "doi": "10.1016/j.celrep.2026.117489",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13713018/",
  "id": "btf3gcf28zkjf",
  "issns": [
    "2211-1247"
  ],
  "landing_url": "https://doi.org/10.1016/j.celrep.2026.117489",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Redox biology and oxidative stress"
    ]
  ],
  "openalex": "W7163540225",
  "pdf_url": null,
  "pmcid": "PMC13713018",
  "pmid": "42241275",
  "published": "2026-06-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/btf3gcf28zkjf.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:29Z",
      "native_id": "PMC13713018",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.celrep.2026.117489"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Redox biology and oxidative stress",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A conserved antioxidant defense at the endoplasmic reticulum membrane",
  "title_text": "A conserved antioxidant defense at the endoplasmic reticulum membrane",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:29Z",
  "url": "https://research.draconitic.com/paper/btf3gcf28zkjf",
  "venue": "Cell reports",
  "versions": []
}