{
  "abstract": "Lipofuscin is a blue-light-absorbing pigment that contributes to oxidative damage. Whether all-trans retinal (atRAL) contributes to its formation in response to light remains unclear. We asked whether blue-light photosensitization of atRAL promotes lipofuscin accumulation in human keratinocytes and whether this depends on Opsin 3 (OPN3). Blue-light excitation of atRAL reduced mitochondrial and lysosomal viability, impaired autophagic flux, and increased lipofuscin. OPN3 knockdown significantly reduced this accumulation. Label-free data-independent acquisition (DIA) proteomics showed that OPN3 acts at three levels. In the dark, OPN3 loss altered proteome networks associated with autophagy, apoptosis, and interferon-related responses. Under blue light, control cells activated a stress-adaptive program spanning inflammatory regulation, lipid metabolism, and mitochondrial function, which atRAL strongly amplified. This molecular signature, including induction of cellular respiration and ATP-production proteins, was largely absent when OPN3 was silenced. Respirometry showed that blue light suppressed oxygen consumption in both lines over the first 24 h, but a faster recovery in OPN3 knockdown cells at 48 and 72 h was observed. Together, these data define three functions of OPN3: maintaining the basal proteome in a blue-light-independent manner, enabling the adaptive blue-light response, and enabling retinal-dependent lipofuscin formation in keratinocytes.",
  "abstract_shown": true,
  "affiliations": [
    "University of Gothenburg (UGOT)"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "M. Von Dentz"
    },
    {
      "name": "H. C. Junqueira"
    },
    {
      "name": "M. A. Herrera Lopez"
    },
    {
      "name": "G. Lisboa"
    },
    {
      "name": "J. Fuchs"
    },
    {
      "name": "K. Tsantarlis"
    },
    {
      "name": "C. Sihlbom Wallem"
    },
    {
      "affs": [
        0
      ],
      "name": "L. V. de Assis"
    },
    {
      "name": "M. d. S. Baptista"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/29y701dqemmm6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.09.750435",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750435v1.full",
  "id": "29y701dqemmm6",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750435v1",
  "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",
      "cell biology"
    ],
    [
      "openalex",
      "1312|Retinal Development and Disorders"
    ]
  ],
  "openalex": "W7213287529",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750435v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/29y701dqemmm6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:32Z",
      "native_id": "10.64898/2026.09.09.750435",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750435v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "OPN3 mediates retinal-dependent lipofuscin accumulation and its loss sensitizes keratinocytes to blue-light-induced proteomic remodeling",
  "title_text": "OPN3 mediates retinal-dependent lipofuscin accumulation and its loss sensitizes keratinocytes to blue-light-induced proteomic remodeling",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:32Z",
  "url": "https://research.draconitic.com/paper/29y701dqemmm6",
  "venue": "bioRxiv",
  "versions": []
}