{
  "abstract": "Mammalian cells execute diverse death programs with distinct immunological consequences. Mitochondrial outer membrane permeabilization (MOMP) drives typically immunologically silent intrinsic apoptosis by releasing cytochrome c and other proapoptotic proteins into the cytosol. Here, we show that MOMP also engages two established repressors of the pyroptosis-inducing NLRP1 inflammasome, oxidized thioredoxin-1 (oxTRX1) and catalytically active DPP8/9, in a coordinated redox and proteostasis program. Immediately after MOMP, oxTRX1 forms a disulfide with MIA40 Cys4 at the MIA40-AIFM1 interface. Subsequently, DPP8/9 cleave AK2, targeting this competing AIFM1 ligand for degradation. Biochemical reconstitution and cryo-EM reveal that oxTRX1 promotes AIFM1 dimerization and preferentially stabilizes MIA40-AIFM1 over AK2-AIFM1. Thus, redox-dependent complex assembly and selective proteolysis converge to favor MIA40-bound AIFM1 after MOMP. These findings suggest how post-MOMP remodeling could reinforce NLRP1 restraint during apoptosis and how disruption of this program could trigger pyroptosis.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "Lydia P. Tsamouri"
    },
    {
      "name": "Michael B. Geeson"
    },
    {
      "name": "Marianna Teplova"
    },
    {
      "name": "Buren Li"
    },
    {
      "name": "Zhencheng Lai"
    },
    {
      "name": "Andrea V. Tellez"
    },
    {
      "name": "Daniel P. Ball"
    },
    {
      "name": "Arpita Chakravarti"
    },
    {
      "name": "Sagnik Sen"
    },
    {
      "name": "M. Jason de la Cruz"
    },
    {
      "name": "Daniel A. Bachovchin",
      "orcid": "0000-0001-8210-1662"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6zs835cp767n1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.761918",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761918v1.full",
  "id": "6zs835cp767n1",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761918v1",
  "language": "en",
  "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"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Cell death mechanisms and regulation"
    ]
  ],
  "openalex": "W7224114472",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761918v1.full.pdf",
  "pmcid": "PMC13733872",
  "pmid": "42990231",
  "published": "2026-10-26",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/6zs835cp767n1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:11Z",
      "native_id": "10.64898/2026.10.26.761918",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761918v1"
    },
    {
      "first_seen": "2026-11-08T12:23:33Z",
      "native_id": "PMC13733872",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.26.761918"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Oxidized TRX1 and DPP8/9 stabilize the MIA40-AIFM1 complex during intrinsic apoptosis",
  "title_text": "Oxidized TRX1 and DPP8/9 stabilize the MIA40-AIFM1 complex during intrinsic apoptosis",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:33Z",
  "url": "https://research.draconitic.com/paper/6zs835cp767n1",
  "venue": "bioRxiv",
  "versions": []
}