| Autor: |
Shishi Li, Huaye Pan, Chao Tan, Yaping Sun, Yanrui Song, Xuan Zhang, Wei Yang, Xuexiang Wang, Dan Li, Yu Dai, Qiang Ma, Chenming Xu, Xufen Zhu, Lijun Kang, Yong Fu, Xuejun Xu, Jing Shu, Naiming Zhou, Feng Han, Dajiang Qin, Wendong Huang, Zhong Liu, Qingfeng Yan |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, Vol 10, Iss 3, Pp 808-821 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2213-6711 |
| DOI: |
10.1016/j.stemcr.2018.01.013 |
| Popis: |
Summary: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young individuals. A potential role of mtDNA mutations in HCM is known. However, the underlying molecular mechanisms linking mtDNA mutations to HCM remain poorly understood due to lack of cell and animal models. Here, we generated induced pluripotent stem cell-derived cardiomyocytes (HCM-iPSC-CMs) from human patients in a maternally inherited HCM family who carry the m.2336T>C mutation in the mitochondrial 16S rRNA gene (MT-RNR2). The results showed that the m.2336T>C mutation resulted in mitochondrial dysfunctions and ultrastructure defects by decreasing the stability of 16S rRNA, which led to reduced levels of mitochondrial proteins. The ATP/ADP ratio and mitochondrial membrane potential were also reduced, thereby elevating the intracellular Ca2+ concentration, which was associated with numerous HCM-specific electrophysiological abnormalities. Our findings therefore provide an innovative insight into the pathogenesis of maternally inherited HCM. : In this article, Yan Q, Liu Z, Huang W, and colleagues show that patient-specific iPSCs as well as their derived cardiomyocytes carrying the m.2336T>C mutation in MT-RNR2 were generated to understand the pathogenic mechanism of maternally inherited HCM. MT-RNR2 mutation resulted in mitochondrial dysfunctions and ultrastructure defects, which induced abnormal Ca2+ homeostasis, then HCM-specific cellular and electrophysiological characteristics in iPSC-CMs. Keywords: mitochondrion, hypertrophic cardiomyopathy, induced pluripotent stem cells, MT-RNR2, maternal inheritance |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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