{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:03:39Z","timestamp":1777943019582,"version":"3.51.4"},"reference-count":54,"publisher":"SAGE Publications","issue":"15-16","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>The study of skeletal muscle disorders in patients with mitochondrial diseases is crucial for gaining insights into disease physiology; however, their molecular mechanisms have not been fully elucidated. We previously established human-induced pluripotent stem (iPS) cells in two patients with the mitochondrial DNA (mtDNA) A3243G mutation and isolated iPS cell clones with either undetectable or high levels of mutations. In the present study, we established skeletal muscle cells from iPS cells with mutation-high and mutation-undetectable clones and comparatively analyzed their mitochondrial functions. Fluorescence immunostaining, fusion index, and qRT-PCR revealed no differences in the morphology, differentiation efficiency, or expression levels of skeletal muscle markers between the mutation-high and mutation-undetectable clones. However, the basal oxygen consumption rate, an indicator of mitochondrial respiration, and adenosine triphosphate (ATP) production were reduced in the mutation-high clones of patients 1 and 2. In addition, the extracellular acidification rate, an indicator of glycolytic activity, was reduced in mutation-high clones of patient 2, who exhibited a more severe clinical phenotype. In the mutation-high clones of both patients, mitochondrial Complex I activity and mtDNA copy number were also reduced, whereas the expression levels of peroxisome proliferator-activated receptor gamma coactivator 1\u03b1 and glucose transporter type 4 were upregulated, indicating compensation for ATP deficiency. These findings reveal the effects of mitochondrial disorders on energy metabolism in skeletal muscles and provide novel insights into skeletal muscle dysfunction in patients with mitochondrial diseases.<\/jats:p>","DOI":"10.1177\/15473287251359330","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:36:22Z","timestamp":1759948582000},"page":"333-342","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Mitochondrial A3243G Mutation on Skeletal Muscle Energy Metabolism: Evidence from Human Induced Pluripotent Stem Cell-Derived Skeletal Muscle Cells"],"prefix":"10.1177","volume":"34","author":[{"given":"Ritsuko","family":"Oikawa","sequence":"first","affiliation":[{"name":"Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junji","family":"Fujikura","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoya","family":"Uchimura","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutoshi","family":"Miyashita","sequence":"additional","affiliation":[{"name":"International University of Health and Welfare, Mita Hospital, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetoshi","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masakatsu","family":"Sone","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-034124"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(06)77003-X"},{"key":"e_1_3_6_4_2","volume-title":"GeneReviews((R))","author":"Chinnery PF","year":"1993","unstructured":"Chinnery PF. 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