{
  "abstract": "Skeletal muscles are composed of multinucleated fibers with distinct metabolic and contractile properties. Skeletal muscles support locomotion and systemic metabolism, and their dysfunction underlies the pathogenesis of muscular dystrophies. The MyoD family inhibitor (Mdfi) has been implicated in muscle biology, yet its function in muscle development and muscle fiber type conversion remains largely unclear. Here, we developed the first tamoxifen (TMX)-inducible, skeletal muscle-specific Mdfi overexpression mouse model using CRISPR/Cas9 and CreERT2 integration, enabling spatiotemporal control of Mdfi activity to mimic therapeutic modulation. This model revealed that Mdfi exerts dual-phase regulatory roles: suppressing early postnatal myogenesis while driving glycolytic-to-oxidative fiber switching in mature muscle. Mechanistically, elevated Mdfi activates the calcium signaling pathway to enhance mitochondrial oxidative phosphorylation, directly linking its function to improved muscle fatigue resistance. These Mdfi overexpression-induced phenotypic alterations exhibit stable transgenerational inheritance patterns. Our findings establish Mdfi as a key regulator of muscle plasticity and metabolic adaptation, providing a genetically tractable model for investigating muscle development and energy metabolism. Importantly, this study opens new avenues for understanding and potentially modulating fiber-type composition in muscular dystrophies and other disorders involving metabolic insufficiency, offering a conceptual framework for future therapeutic interventions aimed at improving muscle health.",
  "abstract_shown": true,
  "affiliations": [
    "National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, Laboratory for Lingnan Modern Agriculture, College of Animal Science, South China Agricultural University, Guangzhou, 510642, Guangdong, China.",
    "Heyuan Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Heyuan, Heyuan, 517000, China.",
    "State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, Guangdong, China.",
    "Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China.",
    "Department of Human Nutrition, Food and Animal Sciences, University of Hawaii at Manoa, Honolulu, HI, 96822, USA.",
    "National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, Laboratory for Lingnan Modern Agriculture, College of Animal Science, South China Agricultural University, Guangzhou, 510642, Guangdong, China. betty@scau.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Tingting Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xulong Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Chao Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Bo Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyuan Mo"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiali Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuezhu Gong"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifan Zhu"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiong Tong"
    },
    {
      "affs": [
        4
      ],
      "name": "Ching Yuan Hu"
    },
    {
      "affs": [
        5
      ],
      "name": "Chong Wang",
      "orcid": "0000-0002-1515-9669"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ajqmshgzrc29e.bib",
  "cited_by": 0,
  "doi": "10.1007/s00018-026-06279-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13719958",
  "id": "ajqmshgzrc29e",
  "issns": [
    "1420-682X",
    "1420-9071"
  ],
  "landing_url": "https://europepmc.org/article/MED/42955098",
  "language": "eng",
  "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": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7172124645",
  "pdf_url": "https://europepmc.org/articles/PMC13719958?pdf=render",
  "pmcid": "PMC13719958",
  "pmid": "42955098",
  "published": "2026-08-01",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/ajqmshgzrc29e.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:47Z",
      "native_id": "MED:42955098",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42955098"
    },
    {
      "first_seen": "2026-11-02T12:23:49Z",
      "native_id": "PMC13719958",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00018-026-06279-x"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Muscle Physiology and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Mdfi overexpression promotes oxidative muscle fiber formation without affecting muscle development in mature skeletal muscles.",
  "title_text": "Mdfi overexpression promotes oxidative muscle fiber formation without affecting muscle development in mature skeletal muscles.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:55Z",
  "url": "https://research.draconitic.com/paper/ajqmshgzrc29e",
  "venue": "Cellular and molecular life sciences : CMLS",
  "versions": []
}