{
  "abstract": "Defective mitophagy is emerging as a key contributor to Alzheimer disease (AD), but the neuronal pathways governing mitochondrial clearance and their contribution to disease progression remain poorly understood. Here, we identify BNIP3L/NIX-dependent mitophagy as a conserved neuronal quality control pathway that maintains mitochondrial fitness and constrains AD-associated proteotoxicity. Loss of BNIP3L/NIX or its C. elegans orthologue DCT-1 impaired basal and stressed-induced mitophagy, disrupted mitochondrial homeostasis, enhanced Tau and Amyloid-beta pathology and compromised neuronal network, synaptic and behavioral function across human neuronal and in vivo models. Conversely, restoring BNIP3L/NIX and DCT-1 activity improved neuronal function under proteotoxic stress in vivo, reduced disease-associated Tau phosphorylation in human neurons and markedly suppressed seeded Tau aggregation in primary mouse neurons. Together, these findings identify BNIP3L/NIX-mediated mitophagy as a mechanistic link between mitochondrial quality control, proteostasis and neuronal function, and establish its restoration as a potential strategy for counteracting AD-associated pathology.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "Y. Li"
    },
    {
      "name": "C. Ploumi"
    },
    {
      "name": "C. Volbracht"
    },
    {
      "name": "W. TIan"
    },
    {
      "name": "N. Kalogeraki"
    },
    {
      "name": "K. Kitopoulou"
    },
    {
      "name": "C. C. Navarro"
    },
    {
      "name": "Z. Li"
    },
    {
      "name": "N. Cherbuin"
    },
    {
      "name": "L. Camargo"
    },
    {
      "name": "Z. Ye"
    },
    {
      "name": "A. J. Nowak"
    },
    {
      "name": "S. Chintawar"
    },
    {
      "name": "M. Z. Cader"
    },
    {
      "name": "L. Berliocchi"
    },
    {
      "name": "S. Goletz"
    },
    {
      "name": "V. Bohr"
    },
    {
      "name": "K. Freude"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Pakalikaras"
    },
    {
      "name": "L. Rasmussen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aa7cbd67xpbts.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.18.759942",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.18.759942v1.full",
  "id": "aa7cbd67xpbts",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.18.759942v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7223005219",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.18.759942v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/aa7cbd67xpbts.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:42Z",
      "native_id": "10.64898/2026.10.18.759942",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.18.759942v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "BNIP3L/NIX-mediated mitophagy limits Alzheimer disease pathology and preserves neuronal function",
  "title_text": "BNIP3L/NIX-mediated mitophagy limits Alzheimer disease pathology and preserves neuronal function",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:42Z",
  "url": "https://research.draconitic.com/paper/aa7cbd67xpbts",
  "venue": "bioRxiv",
  "versions": []
}