The First Center Clinic College of Tianjin Medical University, Tianjin First Center Hospital, Tianjin, China.
Department of Cardiology, Tianjin First Center Hospital, Tianjin, China.
Aging (Albany NY). 2020 Mar 10;12(5):4474-4488. doi: 10.18632/aging.102899.
Myocardial infarction is characterized by sudden ischemia and cardiomyocyte death. Mitochondria have critical roles in regulating cardiomyocyte viability and can sustain damage under ischemic conditions. Mitophagy is a mechanism by which damaged mitochondria are removed by autophagy to maintain mitochondrial structure and function. We investigated the role of the dynamin-like GTPase optic atrophy 1 (Opa1) in mitophagy following myocardial infarction. Opa1 expression was downregulated in infarcted hearts and in hypoxia-treated cardiomyocytes . We found that Opa1 overexpression protected cardiomyocytes against hypoxia-induced damage and enhanced cell viability by inducing mitophagy. Opa1-induced mitophagy was activated by treatment with irisin, which protected cardiomyocytes from further damage following myocardial infarction. Opa1 knockdown abolished the cardioprotective effects of irisin resulting in an enhanced inflammatory response, increased oxidative stress, and mitochondrial dysfunction in cardiomyocytes. Our data indicate that Opa1 plays an important role in maintaining cardiomyocyte viability and mitochondrial function following myocardial infarction by inducing mitophagy. Irisin can activate Opa1-induced mitophagy and protect against cardiomyocyte injury following myocardial infarction.
心肌梗死的特征是突然缺血和心肌细胞死亡。线粒体在调节心肌细胞活力方面起着关键作用，并能在缺血条件下维持损伤。线粒体自噬是一种通过自噬清除受损线粒体以维持线粒体结构和功能的机制。我们研究了动力相关蛋白 1 样 GTP 酶视神经萎缩 1（Opa1）在心肌梗死后线粒体自噬中的作用。Opa1 的表达在梗死心脏中下调，在缺氧处理的心肌细胞中也下调。我们发现，Opa1 的过表达可保护心肌细胞免受缺氧诱导的损伤，并通过诱导线粒体自噬提高细胞活力。Irisin 可激活 Opa1 诱导的线粒体自噬，从而保护心肌细胞免受心肌梗死后的进一步损伤。Opa1 敲低消除了 irisin 的心脏保护作用，导致心肌细胞中炎症反应增强、氧化应激增加和线粒体功能障碍。我们的数据表明，Opa1 通过诱导线粒体自噬在心肌梗死后维持心肌细胞活力和线粒体功能方面发挥重要作用。Irisin 可以激活 Opa1 诱导的线粒体自噬，从而防止心肌梗死后的心肌细胞损伤。
