{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T21:50:02Z","timestamp":1782337802710,"version":"3.54.5"},"reference-count":67,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian National Research, Development and Innovation Office","award":["NKFIH-FK-142481"],"award-info":[{"award-number":["NKFIH-FK-142481"]}]},{"name":"Hungarian National Research, Development and Innovation Office","award":["NKFIH-FK-134684"],"award-info":[{"award-number":["NKFIH-FK-134684"]}]},{"name":"Hungarian National Research, Development and Innovation Office","award":["NKFIH-FK-134235"],"award-info":[{"award-number":["NKFIH-FK-134235"]}]},{"name":"Hungarian National Research, Development and Innovation Office","award":["NKFIH-K-137600"],"award-info":[{"award-number":["NKFIH-K-137600"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["TKP2020-NKA-04"],"award-info":[{"award-number":["TKP2020-NKA-04"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["TKP2021-EGA-28"],"award-info":[{"award-number":["TKP2021-EGA-28"]}]},{"DOI":"10.13039\/501100009232","name":"University of Debrecen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009232","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Debrecen\u2019s Library","award":["OpenA\/DEENK\/342\/2025"],"award-info":[{"award-number":["OpenA\/DEENK\/342\/2025"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Skeletal muscle, constituting 40\u201350% of total body mass, is vital for mobility, posture, and systemic homeostasis. Muscle contraction heavily relies on ATP, primarily generated by mitochondrial oxidative phosphorylation. Mitochondria play a key role in decoding intracellular calcium signals. The endocannabinoid system (ECS), including CB1 receptors (CB1Rs), broadly influences physiological processes and, in muscles, regulates functions like energy metabolism, development, and repair. While plasma membrane CB1Rs (pCB1Rs) are well-established, a distinct mitochondrial CB1R (mtCB1R) population also exists in muscles, influencing mitochondrial oxidative activity and quality control. We investigated the role of mtCB1Rs in skeletal muscle physiology using a novel systemic mitochondrial CB1 deletion murine model. Our in vivo studies showed no changes in motor function, coordination, or grip strength in mtCB1 knockout mice. However, in vitro force measurements revealed significantly reduced specific force in both fast-twitch (EDL) and slow-twitch (SOL) muscles following mtCB1R ablation. Interestingly, knockout EDL muscles exhibited hypertrophy, suggesting a compensatory response to reduced force quality. Electron microscopy revealed significant mitochondrial morphological abnormalities, including enlargement and irregular shapes, correlating with these functional deficits. High-resolution respirometry further demonstrated impaired mitochondrial respiration, with reduced oxidative phosphorylation and electron transport system capacities in knockout mitochondria. Crucially, mitochondrial membrane potential dissipated faster in mtCB1 knockout muscle fibers, whilst mitochondrial calcium levels were higher at rest. These findings collectively establish that mtCB1Rs are critical for maintaining mitochondrial health and function, directly impacting muscle energy production and contractile performance. Our results provide new insights into ECS-mediated regulation of skeletal muscle function and open therapeutic opportunities for muscle disorders and aging.<\/jats:p>","DOI":"10.3390\/cells14191517","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T10:49:34Z","timestamp":1759142974000},"page":"1517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Revealing the Specific Contributions of Mitochondrial CB1 Receptors to the Overall Function of Skeletal Muscle in Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3337-7544","authenticated-orcid":false,"given":"Zolt\u00e1n","family":"Singl\u00e1r","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2621-2282","authenticated-orcid":false,"given":"P\u00e9ter","family":"Szentesi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN Cell Physiology Research Group, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6949-0007","authenticated-orcid":false,"given":"Nyamkhuu","family":"Ganbat","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barnab\u00e1s","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"},{"name":"Centre of Excellence for Interdisciplinary Research, Development and Innovation, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-9572","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Juh\u00e1sz","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8421-4369","authenticated-orcid":false,"given":"M\u00f3nika","family":"G\u00f6nczi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN Cell Physiology Research Group, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-8458","authenticated-orcid":false,"given":"Anik\u00f3","family":"Keller-Pint\u00e9r","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"},{"name":"Centre of Excellence for Interdisciplinary Research, Development and Innovation, University of Szeged, 6720 Szeged, Hungary"},{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4122-5639","authenticated-orcid":false,"given":"Attila","family":"Ol\u00e1h","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"M\u00e1t\u00e9","sequence":"additional","affiliation":[{"name":"Medical GeneTechnology Unit, HUN-REN Institute of Experimental Medicine, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Erd\u00e9lyi","sequence":"additional","affiliation":[{"name":"Medical GeneTechnology Unit, HUN-REN Institute of Experimental Medicine, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-1456","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Csernoch","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN Cell Physiology Research Group, University of Debrecen, 4032 Debrecen, 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