{
  "abstract": "Mitochondrial outer membrane proteins are exploited by diverse intracellular pathogens, to modulate cell metabolism and innate sensing pathways. Here, we demonstrate that TOMM70-dependent mitochondrial recruitment is required to protect SARS-CoV-2 ORF9b from proteasomal degradation, a dependency conserved across ORF9b homologs from related coronaviruses. ORF9b mitochondrial recruitment requires the E477 residue of TOMM70, a surface distinct from that used by the parasite Toxoplasma gondii to engage host mitochondria. We further show that TOMM70 is not a passive scaffold: its depletion activates interferon-stimulated gene expression independently of infection and remodels host immunity distinctly from ORF9b, establishing the receptor and viral protein as mechanistically separable. Using ORF9b-deficient SARS-CoV-2, we demonstrate that ORF9b is dispensable for viral replication and pathological responses in human respiratory epithelial cells and lungs of infected golden Syrian hamsters. Omics profiling of SARS-CoV-2 infected lungs revealed an induction of pathways related to COVID-19 in the absence of ORF9b. Notably, ORF9b-deficient virus-infected lungs show elevated expression of C15ORF48, a nuclear-encoded mitochondrial protein that substitutes for Complex IV subunit NDUFA4 to attenuate inflammation. Collectively, we propose that ORF9b is a receptor-gated viral protein whose principal measurable consequence during authentic infection is a restraint on inflammatory respiratory-chain remodeling.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "Yining Zhao"
    },
    {
      "name": "Lauriane Kergoat"
    },
    {
      "name": "Guilherme Dias de Melo"
    },
    {
      "name": "Florence Larrous"
    },
    {
      "name": "Guillaume Drumont"
    },
    {
      "name": "Juan Diego Hernandez Camacho"
    },
    {
      "name": "Elodie Vimont"
    },
    {
      "name": "Elodie Le Seac’h"
    },
    {
      "name": "Nell Saunders"
    },
    {
      "name": "Martin Kaechele"
    },
    {
      "name": "Etienne Kornobis"
    },
    {
      "name": "Quentin Giai Gianetto"
    },
    {
      "name": "Mariette Matondo"
    },
    {
      "name": "Isabelle Tardieux"
    },
    {
      "name": "Olivier Schwartz"
    },
    {
      "name": "Hervé Bourhy"
    },
    {
      "name": "Timothy Wai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ay4pp0hg9w9j0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.07.13.738231",
  "fulltext_url": null,
  "id": "ay4pp0hg9w9j0",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://pasteur.hal.science/pasteur-05742600v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7168381401",
  "pdf_url": "https://pasteur.hal.science/pasteur-05742600/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-14",
  "publisher": "BioRxiv",
  "ris": "https://research.draconitic.com/paper/ay4pp0hg9w9j0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:31Z",
      "native_id": "pasteur-05742600",
      "source": "hal",
      "url": "https://pasteur.hal.science/pasteur-05742600v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "SARS-CoV-2 ORF9b exploits mitochondrial recruitment to TOMM70 for proteasomal protection and tunes inflammatory remodeling during lung infection",
  "title_text": "SARS-CoV-2 ORF9b exploits mitochondrial recruitment to TOMM70 for proteasomal protection and tunes inflammatory remodeling during lung infection",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:31Z",
  "url": "https://research.draconitic.com/paper/ay4pp0hg9w9j0",
  "venue": "BioRxiv",
  "versions": []
}