@article{2086a4ba68964bcdad9f413d8f75c7e4,
title = "Impaired respiratory function in MELAS-induced pluripotent stem cells with high heteroplasmy levels",
abstract = "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-like episodes (MELAS) is one of the major mitochondrial diseases. The aim of this study was to generate MELAS-specific induced pluripotent stem cells (iPSCs) and to demonstrate that MELAS-iPSCs can be models for mitochondrial disease. We successfully established iPSCs from the primary MELAS-fibroblasts carrying 77.7% of m.3243A>G heteroplasmy. MELAS-iPSC lines ranged from 3.6% to 99.4% of m.3243A>G heteroplasmy levels. The enzymatic activities of mitochondrial respiratory complexes indicated that MELAS-iPSC-derived fibroblasts with high heteroplasmy levels showed a deficiency of complex I activity but MELAS-iPSC-derived fibroblasts with low heteroplasmy levels showed normal complex I activity. Our data indicate that MELAS-iPSCs can be models for MELAS but we should carefully select MELAS-iPSCs with appropriate heteroplasmy levels and respiratory functions for mitochondrial disease modeling.",
keywords = "Disease modeling, IPS cell, MELAS, Mitochondrial disease",
author = "Masaki Kodaira and Hideyuki Hatakeyama and Shinsuke Yuasa and Tomohisa Seki and Toru Egashira and Shugo Tohyama and Yusuke Kuroda and Atsushi Tanaka and Shinichiro Okata and Hisayuki Hashimoto and Dai Kusumoto and Akira Kunitomi and Makoto Takei and Shin Kashimura and Tomoyuki Suzuki and Gakuto Yozu and Masaya Shimojima and Chikaaki Motoda and Nozomi Hayashiji and Yuki Saito and Goto, {Yu ichi} and Keiichi Fukuda",
note = "Funding Information: This study was supported in part by research grants from the Ministry of Education, Culture, Sports, Science, and Technology , Health Labour Sciences Research Grant , the New Energy and Industrial Technology Development Organization, Japan , the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation , Japan Science and Technology Agency , Research Center Network for Realization of Regenerative Medicine “The Program for Intractable Diseases Research utilizing Disease-specific iPS cells” , The Nakatomi Foundation , Japan Heart Foundation/Novartis Grant for Research Award on Molecular and Cellular Cardiology SENSHIN Medical Research Foundation , Kimura Memorial Heart Foundation Research Grant , Japan Intractable Diseases Research Foundation, Japan , and The Cell Science Research Foundation , The Tokyo Biochemical Research Foundation , Suzuken Memorial Foundation , and by Core Research for Evolutional Science and Technology , Japan Science and Technology Agency, Japan. Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
month = apr,
day = "1",
doi = "10.1016/j.fob.2015.03.008",
language = "English",
volume = "5",
pages = "219--225",
journal = "FEBS Open Bio",
issn = "2211-5463",
publisher = "Elsevier BV",
}