{
  "abstract": "Apoptosis-inducing factor is a mitochondrial flavoprotein that links redox metabolism to mitochondrial homeostasis through its interaction with the disulfide relay protein CHCHD4. Although NADH-dependent AIF dimerization has been proposed as the activated state mediating CHCHD4 engagement, whether it is strictly required for productive AIF-CHCHD4 function remains unclear. Here, combining cellular, biochemical and biophysical approaches, we show that disruption of the AIF dimer interface compromises oxidative phosphorylation, respiratory-chain organization and CHCHD4-dependent mitochondrial homeostasis, yet preserves partial AIF function. Our data reveal that the AIF-CHCHD4 system operates as a conformational dynamic redox module in which distinct AIF oligomeric and redox states sustain CHCHD4 activity with different efficiencies. Mechanistically, dimerization is coupled to NADH-dependent conformational changes that regulate coenzyme binding, charge-transfer complex stabilization and catalytic efficiency. In turn, CHCHD4 binding remodels AIF conformational and redox properties, partially compensating for defects in dimer stabilization or redox coupling. Consistently, a peptide derived from the CHCHD4 N-terminus partially restores redox function in a pathogenic AIF variant defective in dimer stabilization, supporting partner-assisted allosteric regulation as a potential therapeutic strategy.",
  "abstract_shown": true,
  "affiliations": [
    "University of Zaragoza"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "O. Soriano"
    },
    {
      "name": "S. Hernandez-Hatibi"
    },
    {
      "name": "R. Gracia-Domingo"
    },
    {
      "name": "S. Romero-Tamayo"
    },
    {
      "name": "M. Ferrer"
    },
    {
      "name": "A. Velazquez-Campoy"
    },
    {
      "name": "J. Marco-Brualla"
    },
    {
      "name": "P. Fernandez-Silva"
    },
    {
      "name": "S. A. Susin"
    },
    {
      "name": "M. Medina"
    },
    {
      "name": "R. Moreno-Loshuertos"
    },
    {
      "affs": [
        0
      ],
      "name": "P. Ferreira Neila"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0agq66v4kk678.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.31.748248",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748248v1.full",
  "id": "0agq66v4kk678",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748248v1",
  "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",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7204887901",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748248v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0agq66v4kk678.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:57Z",
      "native_id": "10.64898/2026.08.31.748248",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748248v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Mitochondrial Function and Pathology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Functional plasticity of AIF revealed by dimerization and CHCHD4 interaction states",
  "title_text": "Functional plasticity of AIF revealed by dimerization and CHCHD4 interaction states",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:57Z",
  "url": "https://research.draconitic.com/paper/0agq66v4kk678",
  "venue": "bioRxiv",
  "versions": []
}