{
  "abstract": "Mitochondrial DNA (mtDNA) damage has been linked to age-related tissue decline, yet its impact on muscle stem cells (MuSCs) integrity remains unclear. Here, we used a dominant-negative variant of the mitochondrial helicase Twinkle (p.K320E) to induce mtDNA instability in C2C12 and MuSCs, and examined myogenic differentiation. In C2C12, mtDNA alterations impaired respiratory complex assembly, increased reactive oxygen species, and disrupted differentiation. Proteomic analyses of differentiated C2C12 revealed extensive remodeling of the mitochondrial proteome. In vivo, during muscle regeneration, MuSCs expressing K320E generated fibers showing mitochondrial dysfunction and elevated oxidative stress. Furthermore, when mtDNA instability was induced during early postnatal stages, mtDNA alterations were progressively transmitted to mature myofibers, resulting in persistent fiber remodeling of the skeletal muscle. Together, these findings identify mtDNA instability in muscle progenitors as a driver of skeletal muscle remodeling and reveal that even modest levels of mtDNA alterations are sufficient to compromise skeletal muscle function.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Ayesha Sen"
    },
    {
      "name": "Olivier Baris"
    },
    {
      "name": "Yulia Schaumkessel"
    },
    {
      "name": "Sebastian Kallabis"
    },
    {
      "name": "Claudie Gabillard-Lefort"
    },
    {
      "name": "Valerie Desquiret"
    },
    {
      "name": "Rudolf Wiesner"
    },
    {
      "name": "David Pla-Martín"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6jmq677t6e49h.bib",
  "cited_by": 0,
  "doi": "10.1016/j.celrep.2026.117979",
  "fulltext_url": null,
  "id": "6jmq677t6e49h",
  "issns": [
    "2211-1247",
    "2211-1247"
  ],
  "landing_url": "https://hal.science/hal-05798800v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7212307901",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-14",
  "publisher": "Elsevier Inc",
  "ris": "https://research.draconitic.com/paper/6jmq677t6e49h.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "hal-05798800",
      "source": "hal",
      "url": "https://hal.science/hal-05798800v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Muscle Physiology and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "mtDNA alterations in muscle progenitors determine myoblast differentiation and disrupt skeletal muscle architecture",
  "title_text": "mtDNA alterations in muscle progenitors determine myoblast differentiation and disrupt skeletal muscle architecture",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/6jmq677t6e49h",
  "venue": "Cell Reports",
  "versions": []
}