{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:54:08Z","timestamp":1785405248637,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,19]]},"group-title":"Molecular Biology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2021-NR058898"],"award-info":[{"award-number":["RS-2021-NR058898"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2023-00219517"],"award-info":[{"award-number":["RS-2023-00219517"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2026-25488310"],"award-info":[{"award-number":["RS-2026-25488310"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"award":["E0210103"],"award-info":[{"award-number":["E0210103"]}],"id":[{"id":"https:\/\/ror.org\/028jp5z02","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 DK129599"],"award-info":[{"award-number":["R01 DK129599"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Copper is an essential trace element for mitochondrial respiration and cellular metabolism, yet its physiological role in skeletal muscle remains incompletely understood. Here, we show that skeletal muscle-specific deletion of the high-affinity copper importer\n                  <jats:italic>Ctr1<\/jats:italic>\n                  (SMKO) in mice causes local copper deficiency, resulting in exercise intolerance, systemic metabolic dysfunction, and hallmarks of mitochondrial myopathy such as ragged-red fibers, lactic acidosis, and aberrant mitochondrial morphology. Mechanistically, copper starvation disrupted the electron transport chain proteome and drove pathological mitochondrial hyperfusion. We identified mitochondrial carrier homolog 2 (MTCH2), an outer mitochondrial membrane protein, as a copper-binding regulator that coordinates mitochondrial copper distribution and morphology. Restoring copper levels via a copper ionophore or AAV-mediated\n                  <jats:italic>Ctr1<\/jats:italic>\n                  re-expression rescued mitochondrial function and alleviated myopathic features in SMKO. These findings uncover the functional coupling of CTR1 and MTCH2 as a critical mechanistic link between copper homeostasis and mitochondrial remodeling required for skeletal muscle function.\n                <\/jats:p>","DOI":"10.1101\/2025.11.19.688750","type":"posted-content","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T17:25:12Z","timestamp":1763573112000},"source":"Crossref","is-referenced-by-count":0,"title":["Copper deficiency drives OXPHOS impairment and mitochondrial hyperfusion via MTCH2 in skeletal muscle"],"prefix":"10.64898","author":[{"given":"Young-Seung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Animal Science, Chonnam National University, Gwangju, Republic of Korea"},{"name":"Host-Directed Antiviral Research Center, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea"},{"name":"Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuc L.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Chonnam National University, Gwangju, Republic of Korea"},{"name":"Host-Directed Antiviral Research Center, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Il","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongmin","family":"Lee","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University, Gwangju, Republic of Korea"},{"name":"College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjong","family":"Moon","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University, Gwangju, Republic of Korea"},{"name":"College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-Oh","family":"Cho","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University, Gwangju, Republic of Korea"},{"name":"College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, USA"},{"name":"Biological Sciences Graduate Program, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyun","family":"Ahn","sequence":"additional","affiliation":[{"name":"Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea"},{"name":"Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5150-4300","authenticated-orcid":false,"given":"Timothy F.","family":"Osborne","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Biomedical Research, Department of Medicine and Biological Chemistry, Johns Hopkin University School of Medicine, St. Petersburg, FL 33701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taner","family":"Duysak","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University, Gwangju, Republic of Korea"},{"name":"Department of Chemistry, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University, Gwangju, Republic of Korea"},{"name":"Department of Chemistry, Chonnam National University, Gwangju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Hwa","family":"Jung","sequence":"additional","affiliation":[{"name":"Aging and Metabolism Research Group, Korea Food Research Institute, 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