Departments of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA; College of Pharmacy, Department of Graduate Research, The Ohio State University, Columbus, Ohio, USA.
Departments of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Mech Ageing Dev. 2020 Jun;188:111245. doi: 10.1016/j.mad.2020.111245. Epub 2020 Apr 11.
Mitochondria are essential organelles that generate energy to fuel myocardial contraction. Accumulating evidence also suggests that, in the heart, mitochondria may contribute to specific aspects of disease progression through the regulations of specific metabolic intermediates, as well as the transcriptional and epigenetic states of cells. If damaged, the mitochondria and their related pathways are hindered, which may result in or contribute to the development of a wide range of cardiovascular diseases. Therefore, the maintenance of cardiac mitochondrial function and integrity through specific mitochondrial quality control mechanisms is critical for cardiovascular health. Mitophagy is part of the overall mitochondrial quality control process, and acts as a specialized autophagic pathway that mediates the lysosomal clearance of damaged mitochondria. In response to cardiac stress and injury, the pathways associated with mitophagy are triggered resulting in the removal of damaged mitochondrial, thereby maintaining cardiac homeostasis. In addition, recent studies have demonstrated an essential role for mitophagy in both developmental and disease-related metabolic transitioning of cardiac mitochondria. Here, we discuss the physiological and the pathological roles of mitophagy in the heart, the underlying molecular mechanisms, as well as potential therapeutic strategies based on mitophagic modulation.
线粒体是产生能量以驱动心肌收缩的重要细胞器。越来越多的证据表明，在心脏中，线粒体可能通过调节特定代谢中间产物以及细胞的转录和表观遗传状态，对疾病进展的特定方面做出贡献。如果受损，线粒体及其相关途径会受到阻碍，这可能导致或促成广泛的心血管疾病的发生。因此，通过特定的线粒体质量控制机制来维持心脏线粒体的功能和完整性对于心血管健康至关重要。线粒体自噬是整体线粒体质量控制过程的一部分，作为一种专门的自噬途径，介导受损线粒体的溶酶体清除。在心脏应激和损伤时，与线粒体自噬相关的途径被触发，导致受损线粒体的清除，从而维持心脏的内稳态。此外，最近的研究表明，线粒体自噬在心脏线粒体发育和疾病相关代谢转换中起着至关重要的作用。在这里，我们讨论了线粒体自噬在心脏中的生理和病理作用、潜在的分子机制，以及基于线粒体自噬调节的潜在治疗策略。
