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Mitochondria are not regulated solely by nuclear genomic DNA but by mitochondrial DNA. It is difficult to develop effective therapies for mitochondrial disease because of the lack of mitochondrial disease models. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke\u2010like episodes (MELAS) is one of the major mitochondrial diseases. The aim of this study was to generate MELAS\u2010specific induced pluripotent stem cells (iPSCs) and to demonstrate that MELAS\u2010iPSCs can be models for mitochondrial disease. We successfully established iPSCs from the primary MELAS\u2010fibroblasts carrying 77.7% of m.3243A&gt;G heteroplasmy. MELAS\u2010iPSC lines ranged from 3.6% to 99.4% of m.3243A&gt;G heteroplasmy levels. The enzymatic activities of mitochondrial respiratory complexes indicated that MELAS\u2010iPSC\u2010derived fibroblasts with high heteroplasmy levels showed a deficiency of complex I activity but MELAS\u2010iPSC\u2010derived fibroblasts with low heteroplasmy levels showed normal complex I activity. Our data indicate that MELAS\u2010iPSCs can be models for MELAS but we should carefully select MELAS\u2010iPSCs with appropriate heteroplasmy levels and respiratory functions for mitochondrial disease modeling.<\/jats:p>","DOI":"10.1016\/j.fob.2015.03.008","type":"journal-article","created":{"date-parts":[[2015,3,30]],"date-time":"2015-03-30T03:30:32Z","timestamp":1427686232000},"page":"219-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Impaired respiratory function in MELAS\u2010induced pluripotent stem cells with high heteroplasmy levels"],"prefix":"10.1002","volume":"5","author":[{"given":"Masaki","family":"Kodaira","sequence":"first","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Hatakeyama","sequence":"additional","affiliation":[{"name":"Department of Mental 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