{
  "abstract": "Intervertebral disc degeneration (IVDD) is driven by progressive loss of nucleus pulposus cell (NPC) homeostasis, yet the stress-responsive mechanisms governing this process remain incompletely defined. Here, we identify a mitochondrial stress–innate immune signalling axis in which impaired mitophagy promotes mitochondrial DNA (mtDNA) leakage, aberrant activation of the cGAS–STING pathway, suppression of the cytoprotective peptide adrenomedullin 2 (ADM2) and consequent NPC senescence and apoptosis. Using integrated transcriptomic analyses, genetic models and human disc specimens, we establish ADM2 as a previously unrecognized downstream effector linking innate immune activation to disc cell fate control. Importantly, we demonstrate that D-allose, a naturally occurring rare sugar with an excellent safety profile, reprogrammes this pathogenic axis by restoring mitophagy, limiting cytosolic mtDNA accumulation, suppressing cGAS–STING signalling and preserving ADM2-dependent cytoprotection. In vivo, D-allose markedly attenuates IVDD, with genetic ablation of STING providing complementary evidence that suppression of this pathway confers robust protection against degeneration. Together, these findings define a mitophagy–mtDNA–cGAS–STING–ADM2 axis as a central regulator of IVDD and reveal D-allose as a physiologically compatible strategy for rebalancing mitochondrial stress signalling and restoring NPC homeostasis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 China",
    "Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou, 510080 PR China",
    "Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 China",
    "Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055 People’s Republic of China",
    "Kinesphere Lab, Irvine High School, 4321 Walnut Ave, Irvine, California 92604 USA",
    "Pain Research Center, Sun Yat-Sen University, Guangzhou, 510080 China",
    "Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zhuoyang Zhao"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jiamin Li"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Linchuan Lei",
      "orcid": "0000-0001-5885-9166"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Yanting Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhe Li"
    },
    {
      "affs": [
        4
      ],
      "name": "Yuhua Zhang"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Zhaomin Zheng"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Hua Wang",
      "orcid": "0000-0002-2605-5697"
    },
    {
      "affs": [
        6
      ],
      "name": "Fan Chen"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Jianru Wang",
      "orcid": "0000-0002-9747-0652"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6036w9hh2smen.bib",
  "cited_by": 0,
  "doi": "10.1038/s12276-026-01844-7",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737178/",
  "id": "6036w9hh2smen",
  "issns": [
    "1226-3613",
    "2092-6413"
  ],
  "landing_url": "https://doi.org/10.1038/s12276-026-01844-7",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2732|Spine and Intervertebral Disc Pathology"
    ]
  ],
  "openalex": "W7214933841",
  "pdf_url": "https://www.nature.com/articles/s12276-026-01844-7.pdf",
  "pmcid": "PMC13737178",
  "pmid": "42816544",
  "published": "2026-10-01",
  "publisher": "Korean Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/6036w9hh2smen.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:27Z",
      "native_id": "PMC13737178",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s12276-026-01844-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2732|Spine and Intervertebral Disc Pathology",
      "subfield": "surgery"
    }
  ],
  "title": "D-allose reprogrammes the mitophagy–mtDNA–cGAS–STING–ADM2 axis to restore nucleus pulposus cell homeostasis in intervertebral disc degeneration",
  "title_text": "D-allose reprogrammes the mitophagy–mtDNA–cGAS–STING–ADM2 axis to restore nucleus pulposus cell homeostasis in intervertebral disc degeneration",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:27Z",
  "url": "https://research.draconitic.com/paper/6036w9hh2smen",
  "venue": "Experimental & Molecular Medicine",
  "versions": []
}