{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:52:22Z","timestamp":1784872342986,"version":"3.55.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Skeletal muscle differentiation in the C2C12 myoblast model requires extensive mitochondrial remodeling to meet rising bioenergetic demands through coordinated changes in biogenesis, dynamics, and respiratory adaptation. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins, improves mitochondrial health, but its role in late-stage myogenic differentiation remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C2C12 myotubes were treated with UA (2 \u03bcM) for 72 h during late-stage differentiation (days 3\u20136). Mitochondrial signaling, respiratory capacity, myogenic morphology, and ultrastructure were assessed by Western blot, high-resolution respirometry, hematoxylin\u2013eosin staining, and transmission electron microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>UA was non-cytotoxic and increased AMPK\u03b1 phosphorylation and PGC-1\u03b1 expression, whereas TOM20, MFN2, and OPA1 were unchanged. Mitophagy\/autophagy-related markers (p-ULK1, p62, BNIP3L\/NIX, LC3-II\/I) were not altered, indicating no detectable changes in steady-state autophagy under the conditions tested. UA selectively increased OXPHOS Complex I and II abundance and enhanced maximal uncoupled respiration, and was associated with increased myotube diameter and myogenic marker abundance. No overt ultrastructural differences were observed by electron microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that UA promotes mitochondrial functional adaptation during myogenic differentiation, with accompanying changes in myogenic phenotype, without clear evidence of altered steady-state mitophagy\/autophagy markers or mitochondrial morphology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1854844","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:38:15Z","timestamp":1782797895000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Urolithin A enhances mitochondrial biogenesis-related markers and maximal respiratory capacity during C2C12 differentiation"],"prefix":"10.3389","volume":"14","author":[{"given":"Ronald","family":"Vargas-Foitzick","sequence":"first","affiliation":[{"name":"Exercise Science Laboratory, School of Kinesiology, Faculty of Medicine, Universidad Finis Terrae","place":["Santiago, Chile"]},{"name":"Escuela de Ciencias de la Salud, Departamento de Kinesiolog\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Irribarra-Tapia","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research, School of Medicine, Faculty of Medicine, Universidad Finis Terrae","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayalen","family":"Valero-Breton","sequence":"additional","affiliation":[{"name":"Exercise and Rehabilitation Sciences Institute, Faculty of Rehabilitation Sciences, School of Physical Therapy, Universidad Andres Bello","place":["Santiago, Chile"]},{"name":"Institute of Health and Sport Sciences, Faculty of Health Science, Universidad Francisco de Vitoria","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Balboa","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research, School of Medicine, Faculty of Medicine, Universidad Finis Terrae","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1111\/cns.13136","article-title":"Urolithin A-activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo","volume":"25","author":"Ahsan","year":"2019","journal-title":"CNS Neurosci. 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