Abstract：
Mitochondria, the membrane-bound cell organelles that supply most of the energy needed for cell function, are highly regulated, dynamic organelles bearing the ability to alter both form and functionality rapidly to maintain normal physiological events and challenge stress to the cell. This amazingly vibrant movement and distribution of mitochondria within cells is controlled by the highly coordinated interplay between mitochondrial dynamic processes and fission and fusion events, as well as mitochondrial quality-control processes, mainly mitochondrial autophagy (also known as mitophagy). Fusion connects and unites neighboring depolarized mitochondria to derive a healthy and distinct mitochondrion. In contrast, fission segregates damaged mitochondria from intact and healthy counterparts and is followed by selective clearance of the damaged mitochondria via mitochondrial specific autophagy, i.e., mitophagy. Hence, the mitochondrial processes encompass all coordinated events of fusion, fission, mitophagy, and biogenesis for sustaining mitochondrial homeostasis. Accumulated evidence strongly suggests that mitochondrial impairment has already emerged as a core player in the pathogenesis, progression, and development of various human diseases, including cardiovascular ailments, the leading causes of death globally, which take an estimated 17.9 million lives each year. The crucial factor governing the fission process is the recruitment of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, from the cytosol to the outer mitochondrial membrane in a guanosine triphosphate (GTP)-dependent manner, where it is oligomerized and self-assembles into spiral structures. In this review, we first aim to describe the structural elements, functionality, and regulatory mechanisms of the key mitochondrial fission protein, Drp1, and other mitochondrial fission adaptor proteins, including mitochondrial fission 1 (Fis1), mitochondrial fission factor (Mff), mitochondrial dynamics 49 (Mid49), and mitochondrial dynamics 51 (Mid51). The core area of the review focuses on the recent advances in understanding the role of the Drp1-mediated mitochondrial fission adaptor protein interactome to unravel the missing links of mitochondrial fission events. Lastly, we discuss the promising mitochondria-targeted therapeutic approaches that involve fission, as well as current evidence on Drp1-mediated fission protein interactions and their critical roles in the pathogeneses of cardiovascular diseases (CVDs).
摘要：
线粒体,提供细胞功能所需大部分能量的膜结合细胞细胞器，受到高度管制，动态细胞器具有快速改变形式和功能的能力，以维持正常的生理事件并挑战细胞的压力。线粒体在细胞内的这种令人惊讶的充满活力的运动和分布是由线粒体动态过程与裂变和融合事件之间高度协调的相互作用控制的。以及线粒体质量控制过程，主要是线粒体自噬(又称线粒体自噬)。融合将相邻的去极化线粒体连接并联合起来，以获得健康且独特的线粒体。相比之下,裂变将受损的线粒体与完整和健康的线粒体分离，然后通过线粒体特异性自噬选择性清除受损的线粒体，即，线粒体自噬.因此，线粒体过程包含所有协调的融合事件，裂变,线粒体自噬,和维持线粒体稳态的生物发生。积累的证据强烈表明，线粒体损伤已经成为发病机理的核心参与者，programming,以及各种人类疾病的发展，包括心血管疾病,全球主要的死亡原因，估计每年夺走1790万人的生命。控制裂变过程的关键因素是动态蛋白相关蛋白1（Drp1）的募集，一种调节线粒体裂变的GTP酶，从胞质溶胶到线粒体外膜的三磷酸鸟苷（GTP）依赖性方式，它被寡聚化并自组装成螺旋结构。在这次审查中,我们首先要描述的结构元素，功能，和关键线粒体裂变蛋白的调节机制，Drp1和其他线粒体裂变衔接蛋白，包括线粒体裂变1(Fis1)，线粒体裂变因子（Mff），线粒体动力学49（Mid49），和线粒体动力学51(Mid51)。这篇综述的核心领域集中在理解Drp1介导的线粒体裂变衔接蛋白相互作用组对揭示线粒体裂变事件缺失环节的作用方面的最新进展。最后,我们讨论了有希望的线粒体靶向治疗方法，涉及裂变，以及目前关于Drp1介导的裂变蛋白相互作用及其在心血管疾病（CVDs）发病机制中的关键作用的证据。
