Zhang Jing, Zhang Feng, Wang Yanou
Department of Cardiology, Tianjin First Central Hospital, Tianjing, China.
Health Management Department, Tianjin First Central Hospital, Tianjing, China.
Front Physiol. 2021 Jul 8;12:707634. doi: 10.3389/fphys.2021.707634. eCollection 2021.
Diabetic cardiomyopathy has been associated with mitochondrial damage. Mitochondria-endoplasmic reticulum (ER) contact is an important determinant of mitochondrial function and ER homeostasis. We therefore investigated whether hyperglycemia can damage the mitochondria by increasing their contact with the ER in cardiomyocytes. We found that hyperglycemia induced mitochondria-ER contact in cardiomyocytes, as evidenced by the increased MMM1, MDM34, and BAP31 expressions. Interestingly, the silencing of reduced the cooperation between the mitochondria and the ER in cardiomyocytes. silencing improved cardiomyocyte viability and function under hyperglycemic conditions. Additionally, the silencing of markedly attenuated the release of calcium from the ER to the mitochondria, thereby preserving mitochondrial metabolism in cardiomyocytes under hyperglycemic conditions. silencing reduced mitochondrial reactive oxygen species production, which reduced mitochondria-dependent apoptosis in hyperglycemia-treated cardiomyocytes. Finally, silencing attenuated ER stress in cardiomyocytes subjected to high-glucose stress. These results demonstrate that Mfn2 promotes mitochondria-ER contact in hyperglycemia-treated cardiomyocytes. The silencing of sustained mitochondrial function, suppressed mitochondrial calcium overload, prevented mitochondrial apoptosis, and reduced ER stress, thereby enhancing cardiomyocyte survival under hyperglycemic conditions.
糖尿病性心肌病与线粒体损伤有关。线粒体-内质网（ER）接触是线粒体功能和内质网稳态的重要决定因素。因此，我们研究了高血糖是否会通过增加心肌细胞中线粒体与内质网的接触来损伤线粒体。我们发现高血糖诱导心肌细胞中线粒体-内质网接触，MMM1、MDM34和BAP31表达增加证明了这一点。有趣的是，沉默[具体基因]可减少心肌细胞中线粒体与内质网之间的协作。沉默[具体基因]可改善高血糖条件下心肌细胞的活力和功能。此外，沉默[具体基因]显著减弱了钙从内质网向线粒体的释放，从而在高血糖条件下维持心肌细胞中的线粒体代谢。沉默[具体基因]减少了线粒体活性氧的产生，这减少了高血糖处理的心肌细胞中线粒体依赖性凋亡。最后，沉默[具体基因]减轻了高糖应激心肌细胞中的内质网应激。这些结果表明，Mfn2在高血糖处理的心肌细胞中促进线粒体-内质网接触。沉默[具体基因]维持了线粒体功能，抑制了线粒体钙超载，防止了线粒体凋亡，并减轻了内质网应激，从而在高血糖条件下提高了心肌细胞的存活率。
