{
  "abstract": "The endoplasmic reticulum (ER) coordinates protein folding and lipid biosynthesis, while peroxisomes govern fatty-acid catabolism and redox balance. However, little is known about the mechanisms by which these organelles communicate. Here we show that activating transcription factor 6 (ATF6), a cytoprotective ER-resident sensor of the unfolded protein response (UPR), forms a molecular tether that zippers the ER and peroxisomes together at a 23-nm intermembrane distance. ATF6 achieves this by inserting a short segment of its unstructured N-terminal cytosolic tail into the solvated transmembrane cavity of the peroxisomal ABC-type lipid transporter ABCD3, trapping it in an off-state. This interaction is reinforced by Ceapin, a previously identified small molecule molecular-glue ligand, which promotes ER-peroxisome contact formation. The junctions serve as a scaffold that can initiate peroxisome turnover by p62-triggered autophagy (pexophagy), as enhanced lipid processing resulting from organelle zippering leads to peroxisome damage due to excessive reactive oxygen species (ROS) accumulation. These findings define ATF6 as a non-transcriptional regulator of organelle quality control and provide a template for engineering Ceapin analogues against ATF6/ABCD3-dependent colorectal and hepatocellular cancers and related diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Altos Labs; Buck Institute for Research on Aging (current)"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "C. M. Noddings"
    },
    {
      "name": "R. Mukherjee"
    },
    {
      "name": "C. Peukert"
    },
    {
      "name": "T. G. Laughlin"
    },
    {
      "name": "J. Wang"
    },
    {
      "name": "B. T. Walters"
    },
    {
      "name": "T.-W. Lu"
    },
    {
      "name": "T. Croll"
    },
    {
      "name": "D. Eismann"
    },
    {
      "name": "S. Harel"
    },
    {
      "name": "A. Xu"
    },
    {
      "name": "K. Kim"
    },
    {
      "name": "M. Gupta"
    },
    {
      "name": "J. Crawford"
    },
    {
      "name": "C. P. Arthur"
    },
    {
      "name": "D. Itzhak"
    },
    {
      "name": "M. Costa-Mattioli"
    },
    {
      "name": "J. Rudolph"
    },
    {
      "name": "A. Ashkenazi"
    },
    {
      "affs": [
        0
      ],
      "name": "P. Walter"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bvs9c6ftmzh7a.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.05.756567",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756567v1.full",
  "id": "bvs9c6ftmzh7a",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756567v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "1307|Endoplasmic Reticulum Stress and Disease"
    ]
  ],
  "openalex": "W7220687196",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756567v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bvs9c6ftmzh7a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:13Z",
      "native_id": "10.64898/2026.10.05.756567",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756567v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Peroxisome quality control is gated by a dynamic ATF6α-ABCD3 tether",
  "title_text": "Peroxisome quality control is gated by a dynamic ATF6α-ABCD3 tether",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:13Z",
  "url": "https://research.draconitic.com/paper/bvs9c6ftmzh7a",
  "venue": "bioRxiv",
  "versions": []
}