Cardiac dysfunction due to mitochondrial impairment assessed by human iPS cells caused by DNM1L mutations
DNM1L mutations was identified in two pediatric patients who developed cardiac dysfunction and human induced pluripotent stem cells (hiPSCs) were established from these two patients and differentiated into hiPSC-derived cardiomyocytes (hiPS-CMs). DNM1L mutations induced abnormal mitochondrial morphology, mitochondrial dysfunction, and insufficient ATP production in hiPS-CMs. In addition, hiPS-CMs with DNM1L mutation showed abnormal Ca<sup>2+</sup> kinetics and impaired contractile and diastolic function. This is the first study that elucidate the mechanism of cardiac dysfunction caused by DNM1L mutations by using hiPSCs.
Authors
- Taro Yamazaki
- Yuko Akioka
- Takeshi Adachi (ORCID: https://orcid.org/0000-0002-8642-8993)
- Akira Ohtake (ORCID: https://orcid.org/0000-0003-1147-3113)
- Hidetoshi Hagiwara
- Megumu K. Saito (ORCID: https://orcid.org/0000-0001-8813-3614)
- Hiroko Harashima
- Ikuroh Ohsawa (ORCID: https://orcid.org/0000-0002-7212-9298)
- Yasunori Fujita (ORCID: https://orcid.org/0009-0006-0334-7212)
- Ikuro Suzuki (ORCID: https://orcid.org/0000-0002-1653-1450)
- Masataka Ito (ORCID: https://orcid.org/0000-0002-0018-4247)
- Daisuke Yoshinaga (ORCID: https://orcid.org/0000-0003-0484-510X)
- Yoshiteru Tamura
- Shigeaki Nonoyama (ORCID: https://orcid.org/0000-0001-9698-366X)
- Tetsuya Kitaguchi (ORCID: https://orcid.org/0000-0001-6701-1933)
- Junya Take
- Shiro Baba (ORCID: https://orcid.org/0000-0001-6253-6087)
- Kazuki Kagami (ORCID: https://orcid.org/0000-0002-1743-4409)
- Shoichiro Tateishi
- Kei Murayama (ORCID: https://orcid.org/0000-0002-3923-8636)
- Satoshi Arai (ORCID: https://orcid.org/0000-0003-4807-8248)
- Madori Osawa (ORCID: https://orcid.org/0009-0001-1262-5484)
- Mitsujiro Osawa (ORCID: https://orcid.org/0000-0001-6761-7054)
- Kohsuke Imai (ORCID: https://orcid.org/0000-0003-2132-8403)
- F. Hirose
- Shiro Matsumoto
Institutions
- Kanazawa University (JP)
- Tohoku Institute of Technology (JP)
- Tokyo Institute of Technology (JP)
- Jichi Medical University (JP)
- Kyoto University (JP)
- Juntendo University (JP)
- Life Science Institute (JP)
- Chiba Hospital (JP)
- Tokyo Metropolitan Institute of Gerontology (JP)
- Jichi Medical University Saitama Medical Center (JP)
- National Defense Medical College (JP)
- Saitama Medical University (JP)
- Kumamoto University (JP)
Publication Details
- Journal
- Pediatric Research
- Published
- 2025-04-23
- DOI
- https://doi.org/10.1038/s41390-025-04045-6
- Citations
- 2
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Japan Agency for Medical Research and Development
- National Defense Medical College
- Research Promotion Foundation
- Mother and Child Health Foundation
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency