{
  "abstract": "Verteporfin (VP) is widely used as a light-independent pharmacologic inhibitor of the YAP-TEAD transcriptional complex, despite its potent photosensitizing properties. Here we show that VP-associated high–molecular–weight complexes and apparent depletion of key proteins on immunoblots can be substantially driven by ambient-light exposure during post-lysis handling, more than by light during cellular treatment. In this study, the hypothesis is tested independently using MEL270, HEK293, and MCF-7 cells treated with therapeutic and supra-therapeutic concentrations of VP under four systematically varied light/dark conditions. The results demonstrate that high-molecular-weight complex (HMWC) formation for p62, DIAP1, ROCK1, YAP, and phospho-YAP is driven principally by light exposure during sample processing rather than during cell treatment, occurs in cell-free lysates within 1 hour of ambient-light exposure, and is markedly attenuated by both N-acetylcysteine and L-histidine, consistent with contributions from both radical-mediated and singlet oxygen-mediated photochemistry. Notably, YAP and phospho-YAP are highly susceptible to photo-cross-linking, whereas transcription enhancer factor 1 (TEF1)/TEAD1 remains comparatively resistant, a pattern that mimics selective YAP-TEAD inhibition on standard immunoblots. In a single-experiment CCK-8 assay, viability was markedly lower under light than in darkness at 24 hours, an observation consistent with the immunoblot findings but requiring independent replication. These findings support the light-artifact hypothesis and may have implications for how preclinical data on VP are interpreted in the design of clinical investigations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, Retina Service, Ines and Frederick Yeatts Lab in Retina Research, MassachusettsEye and Ear, Harvard Medical School, Boston, Massachusetts, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Konstantinos G. Baroutis"
    },
    {
      "name": "Victor San Martin C. Corrêa"
    },
    {
      "name": "Dimitrios Ntentakis"
    },
    {
      "name": "Toshio Narimatsu"
    },
    {
      "name": "Evangelos S. Gragoudas"
    },
    {
      "name": "Joan W. Miller"
    },
    {
      "name": "Lucy H. Young"
    },
    {
      "name": "Demetrios G. Vavvas"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0ykzmjkkrpmcx.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358654",
  "fulltext_url": null,
  "id": "0ykzmjkkrpmcx",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0358654",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1307|Hippo pathway signaling and YAP/TAZ"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Amino acids/Sulfur containing amino acids/Methionine"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Tissue repair/Lysis (medicine)"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmacology/Routes of administration/Intravenous injections"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Amino acids/Sulfur containing amino acids/Methionine"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical compounds/Sulfoxides"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical elements/Oxygen"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Amino acids/Sulfur containing amino acids/Methionine"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Physical chemistry/Chemical bonding/Cross-linking"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Physical chemistry/Photochemistry"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Electromagnetic radiation/Light"
    ]
  ],
  "openalex": "W7131810585",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358654&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/0ykzmjkkrpmcx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pone.0358654",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0358654"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "plos:physical chemistry",
      "subfield": "physical"
    },
    {
      "field": "medicine",
      "origin": "plos:pharmacology",
      "subfield": "pharmacology-toxicology"
    },
    {
      "field": "medicine",
      "origin": "plos:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Ambient light drives verteporfin-induced protein cross-linking during standard laboratory sample processing",
  "title_text": "Ambient light drives verteporfin-induced protein cross-linking during standard laboratory sample processing",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/0ykzmjkkrpmcx",
  "venue": "PLOS One",
  "versions": []
}