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Chronic activation of the aryl hydrocarbon receptor (AHR) by tobacco smoke impairs skeletal muscle mitochondrial function. Here, we evaluated whether E\u2010cig vapor elicits AHR activation and mitochondrial dysfunction in skeletal muscle. C2C12 mouse myoblasts were exposed to 1% dimethyl sulfoxide (vehicle), 0.02% tobacco\u2010smoke condensate (TSC), or vape condensate (VC) at 0.006%, 0.06%, and 0.3%. Cell viability, AHR\u2010pathway gene expression (\n                    <jats:italic>Ahr<\/jats:italic>\n                    ,\n                    <jats:italic>Ahrr<\/jats:italic>\n                    ,\n                    <jats:italic>Cyp1a1<\/jats:italic>\n                    ), and mitochondrial respiration were assessed. Male C57BL\/6J mice (12\u201316\u2009weeks;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094\u20135\/group) underwent acute 2\u2010h or 4\u2010week exposure to room air, tobacco smoke, or E\u2010cig vapor. Serum cotinine, gastrocnemius AHR\u2010pathway genes, muscle contractility, and mitochondrial function were evaluated. In myoblasts, 0.02% TSC and 0.3% VC upregulated\n                    <jats:italic>Ahrr<\/jats:italic>\n                    and\n                    <jats:italic>Cyp1a1<\/jats:italic>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and reduced complex I state\u20103 respiration (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) without affecting viability. In mice, acute exposure to tobacco smoke and E\u2010cig vapor significantly increased serum cotinine (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), but only tobacco\u2010smoke activated AHR\u2010pathway. Chronic exposure to tobacco smoke and E\u2010cig vapor reduced mitochondrial complex I and II state\u20103 respiration (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), without altering muscle contractile function. These findings suggest that AHR\u2010independent mechanisms contribute to mitochondrial dysfunction with E\u2010cig vapor exposure.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70797","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:15:58Z","timestamp":1773008158000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["E\u2010cigarette exposure impairs skeletal muscle mitochondrial function in male mice"],"prefix":"10.14814","volume":"14","author":[{"given":"Pavel","family":"Mazirka","sequence":"first","affiliation":[{"name":"Division of Vascular Surgery and Endovascular Therapy University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaewon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascual","family":"Jahuey","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery and Endovascular Therapy University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerri A.","family":"O'Malley","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery and Endovascular Therapy University of Florida  Gainesville Florida USA"},{"name":"North Florida\/South Georgia Veterans Health System Malcom Randall VA Medical Center  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott T.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery and Endovascular Therapy University of Florida  Gainesville Florida USA"},{"name":"North Florida\/South Georgia Veterans Health System Malcom Randall VA Medical Center  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore T.","family":"Scali","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery and Endovascular Therapy University of Florida  Gainesville Florida USA"},{"name":"North Florida\/South Georgia Veterans Health System Malcom Randall VA Medical Center  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-029X","authenticated-orcid":false,"given":"Terence E.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott A.","family":"Berceli","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery and Endovascular Therapy University of Florida  Gainesville Florida USA"},{"name":"North Florida\/South Georgia Veterans Health System Malcom Randall VA Medical Center  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-6469","authenticated-orcid":false,"given":"Kyoungrae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida 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