{
  "abstract": "Marfan syndrome (MFS) causes thoracic aortic aneurysm through mutations in the fibrillin-1 gene and subsequent dysregulated TGF-{beta} signalling. Mixed lineage kinase domain-like protein (MLKL) executes necroptosis after RIPK3-dependent phosphorylation, but also functions in endosomal trafficking. Here we show that MLKL phosphorylation sustains TGF-{beta} receptor recycling and aortic wall integrity without causing cell death. Phosphorylation-dead MLKLS345A/S347A (MlklAA) mice developed aortic root dilation with disorganised collagen architecture and a secretory-pathway proteomic signature. Crossing them with Fbn1C1039G/+ MFS mice aggravated aortic dilation, disrupted collagen fibril ultrastructure and prolyl/lysyl hydroxylation, and caused lethal rupture under angiotensin II. Complete MLKL deficiency reproduced this phenotype. Phosphorylated MLKL was increased in MFS aortas, yet cleaved caspase-3, TUNEL positivity, smooth muscle cell content and leukocyte infiltration were unchanged. In smooth muscle cells, MLKL depletion dysregulated collagen-modifying enzymes, altered TGF-{beta}-driven matrix remodelling and impaired RAB11-dependent TGF{beta}R1 recycling. These findings suggest that phosphorylation-dependent, non-lytic functions of MLKL may contribute to the maintenance of thoracic aortic integrity in MFS.",
  "abstract_shown": true,
  "affiliations": [
    "Department III of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "H. Nemade"
    },
    {
      "name": "H. Guthoff"
    },
    {
      "name": "O. Zimmermann"
    },
    {
      "name": "S. Riemen"
    },
    {
      "name": "H. Stiller"
    },
    {
      "name": "M. Hedbawny"
    },
    {
      "name": "B. Agbowo"
    },
    {
      "name": "D. Zahnow"
    },
    {
      "name": "F. Holtkamp"
    },
    {
      "name": "P. Arkenberg"
    },
    {
      "name": "D. Mehrkens"
    },
    {
      "name": "P. Jahn"
    },
    {
      "name": "F. S. Nettersheim"
    },
    {
      "name": "P. Schelemei"
    },
    {
      "name": "F. R. Picard"
    },
    {
      "name": "K. M. Lagunas"
    },
    {
      "name": "J. Jayachandran"
    },
    {
      "name": "G. Sengle"
    },
    {
      "name": "U. Ros"
    },
    {
      "name": "H. Winkels"
    },
    {
      "name": "T. Riffelmacher"
    },
    {
      "name": "S. Baldus"
    },
    {
      "name": "A. J. Garcia-Saez"
    },
    {
      "name": "M. Adam"
    },
    {
      "name": "M. Mollenhauer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fd02kpm1999y7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.757966",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757966v1.full",
  "id": "fd02kpm1999y7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757966v1",
  "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",
      "1311|Connective tissue disorders research"
    ]
  ],
  "openalex": "W7221720471",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757966v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fd02kpm1999y7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:33Z",
      "native_id": "10.64898/2026.10.09.757966",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757966v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "A cell death-independent role for MLKL in TGF-β receptor recycling in Marfan syndrome",
  "title_text": "A cell death-independent role for MLKL in TGF-β receptor recycling in Marfan syndrome",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:33Z",
  "url": "https://research.draconitic.com/paper/fd02kpm1999y7",
  "venue": "bioRxiv",
  "versions": []
}