Malfunction of myocardial mitochondria plays a crucial role in the development of cardiovascular disorders, especially hypertrophic and dilated cardiomyopathies. Cardiac troponin I (cTnI) is an important structural protein and essential to contraction and relaxation of cardiomyocytes. Recent studies suggest that mutated cTnIR193H could function as a regulatory molecule for other cell functions. This study was to determine whether mutated cTnI could contribute to mitochondrial dysfunction of cardiomyocytes. Primary cardiomyocytes were transfected with cTnIR193H adenovirus with empty vector as control. Mitochondrial structure and function were evaluated in the cells 72 h after transfection. Transmission electron microscopy examination showed mitochondria in the cardiomyocytes with R193H mutation displayed broken cristae, vacuolation, and mitophagy. Mitochondrial function studies revealed a significant decrease in complex I activity, ATP and reactive oxygen species levels, and oxygen consumption rate compared with controls. Western blot analysis demonstrated that expressions of mitochondria-related genes, including ND5 (ubiquinone oxidoreductase chain 5), LRPPRC (a leucine-rich protein of pentatricopeptide repeat family), and PGC-1α (PPARG co-activator 1 alpha), were significantly downregulated in R193H mutation cardiomyocytes compared with the control. Swelling and broken cristae were observed in the mitochondria of cardiomyocytes from cTnIR193H mutation transgenic mice with decreased mitochondrial function, not from the littermate control mice. The data from the present study demonstrated that mitochondrial structure and function were significantly impaired in cardiomyocytes with cTnIR193H mutation, suggesting that cTnI might be critically involved in maintaining the structural and functional integrity of myocardial mitochondria.

中文翻译：

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心肌肌钙蛋白I R193H突变与心肌细胞线粒体损伤有关。

心肌线粒体功能异常在心血管疾病尤其是肥大性和扩张型心肌病的发展中起着至关重要的作用。心肌肌钙蛋白I（cTnI）是一种重要的结构蛋白，对于心肌细胞的收缩和松弛至关重要。最近的研究表明，突变的cTnIR193H可以作为其他细胞功能的调节分子。这项研究是为了确定突变的cTnI是否可能导致心肌细胞的线粒体功能障碍。用空载体作为对照，用cTnIR193H腺病毒转染原代心肌细胞。转染72小时后，评估细胞中的线粒体结构和功能。透射电子显微镜检查显示具有R193H突变的心肌细胞中的线粒体显示出cr裂，空泡化和线粒体。线粒体功能研究显示，与对照组相比，复杂I活性，ATP和活性氧水平以及耗氧率显着降低。Western印迹分析表明，线粒体相关基因（包括ND5（泛醌氧化还原酶链5），LRPPRC（​​富含五聚肽的亮氨酸的重复序列家族）和PGC-1α（PPARG共激活因子1 alpha）的表达明显下调。与对照相比，R193H突变型心肌细胞中的α-淀粉样蛋白。在具有降低的线粒体功能的cTnIR193H突变转基因小鼠的心肌细胞的线粒体中观察到肿胀和broken裂，而不是来自同窝对照小鼠。