{
  "abstract": "Autophagy is initiated at endoplasmic reticulum (ER)-associated omegasomes, yet how the ER contributes to mitochondrial cargo degradation during early autophagosome formation remains unclear. Gp78 is an ER-resident RING E3 ubiquitin ligase involved in ER-associated degradation (ERAD) that also promotes Parkin-independent mitophagy. However, the spatial relationship between Gp78 ubiquitin ligase activity, omegasome formation, and mitochondrial degradation has yet to be defined. Combining targeted mitochondria labeling and super-resolution STED microscopy, we show that the Gp78 ubiquitin ligase is localized to and regulates DFCP1-positive omegasome formation, where it drives mitochondrial protein breakdown. Using fluorescent mitophagy reporters and acute ivermectin-induced mitophagy, generation of mitophagy intermediates lacking mitochondrial outer membrane (TOMM20) was found to be dependent on the Gp78 RING finger as well as the BAG6-UBL4A-USP13 ubiquitin-ligase module, and independent of PINK1 and Parkin. Object-based analysis of 3D STED images further showed that both DFCP1- and LC3-positive structures associate primarily with intact mitochondrial fragments which show progressive degradation of mitochondrial content. Gp78 localizes to and promotes, via BAG6, the formation of DFCP1-positive omegasomes and mitochondrial protein degradation in these early autophagic structures. ER-derived omegasome biogenesis is therefore coupled to Gp78-dependent ubiquitin ligase activity and local degradation of mitochondrial cargo during mitophagy.",
  "abstract_shown": true,
  "affiliations": [
    "University of British Columbia"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "M. Ortiz-Silva"
    },
    {
      "name": "B. Joshi"
    },
    {
      "name": "J. Zheng"
    },
    {
      "name": "R. Takimoto"
    },
    {
      "name": "S. Chopra"
    },
    {
      "name": "N. Yachie"
    },
    {
      "name": "G. Hamarneh"
    },
    {
      "affs": [
        0
      ],
      "name": "I. R. Nabi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1jrn9ptmfw4es.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.04.749530",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749530v1.full",
  "id": "1jrn9ptmfw4es",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749530v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7211935633",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749530v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1jrn9ptmfw4es.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:07Z",
      "native_id": "10.64898/2026.09.04.749530",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749530v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "The Gp78 ubiquitin E3 ligase drives mitophagy by regulating omegasome formation",
  "title_text": "The Gp78 ubiquitin E3 ligase drives mitophagy by regulating omegasome formation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:07Z",
  "url": "https://research.draconitic.com/paper/1jrn9ptmfw4es",
  "venue": "bioRxiv",
  "versions": []
}