{
  "abstract": "The Voltage-Dependent Anion Channel (VDAC) forms a unique pathway across the mitochondrial outer membrane for small ions and water-soluble metabolites, such as ATP and ADP. Despite VDAC's involvement in both normal regulation of respiration and in a wide variety of mitochondria-associated pathologies, there are, surprisingly, no known FDA-approved pharmacological agents targeting VDAC. Earlier, we have shown that VDAC can be regulated through its interactions with well-known cytosolic proteins--dimeric tubulin and -synuclein (Syn)--that are able to reversibly block this channel at nanomolar concentrations. We hypothesized that the architecture of a prospective VDAC inhibitor should fulfill two main requirements: possess a negatively charged disordered polypeptide C- or N-terminus as a pore blocking domain and feature a mitochondrial membrane-binding domain. Using Syn as a template, we engineered three peptides and demonstrated that they all characteristically block VDAC reconstituted into planar lipid membranes in a controllable manner, thereby mimicking the actions of tubulin and Syn. The VDAC blockage times induced by the synthetic peptides are comparable to Syn-induced blockages, though the half-effect solution concentration for synthetic blockers is a hundred times higher than that of Syn. Our work can be considered a proof-of-principle study that informs future development of mitochondria-targeting pharmacological tools.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Tatiana K. Rostovtseva",
      "orcid": "0000-0001-7299-7362"
    },
    {
      "name": "Philip A. Gurnev"
    },
    {
      "name": "David P. Hoogerheide",
      "orcid": "0000-0003-2918-1469"
    },
    {
      "name": "Sergey M. Bezrukov",
      "orcid": "0000-0002-8209-8050"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cebzhgvz1td1f.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.13.758907",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758907v1.full",
  "id": "cebzhgvz1td1f",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758907v1",
  "language": "en",
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7223068179",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758907v1.full.pdf",
  "pmcid": "PMC13738398",
  "pmid": "42995798",
  "published": "2026-10-13",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/cebzhgvz1td1f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:40Z",
      "native_id": "10.64898/2026.10.13.758907",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758907v1"
    },
    {
      "first_seen": "2026-11-09T12:23:23Z",
      "native_id": "PMC13738398",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.13.758907"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Towards VDAC pharmacology: Developing small-peptide channel inhibitors inspired by nature",
  "title_text": "Towards VDAC pharmacology: Developing small-peptide channel inhibitors inspired by nature",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:23Z",
  "url": "https://research.draconitic.com/paper/cebzhgvz1td1f",
  "venue": "bioRxiv",
  "versions": []
}