Ong Sang-Bing, Kalkhoran Siavash Beikoghli, Hernández-Reséndiz Sauri, Samangouei Parisa, Ong Sang-Ging, Hausenloy Derek John
Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore.
National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.
Cardiovasc Drugs Ther. 2017 Feb;31(1):87-107. doi: 10.1007/s10557-016-6710-1.
Mitochondrial health is critically dependent on the ability of mitochondria to undergo changes in mitochondrial morphology, a process which is regulated by mitochondrial shaping proteins. Mitochondria undergo fission to generate fragmented discrete organelles, a process which is mediated by the mitochondrial fission proteins (Drp1, hFIS1, Mff and MiD49/51), and is required for cell division, and to remove damaged mitochondria by mitophagy. Mitochondria undergo fusion to form elongated interconnected networks, a process which is orchestrated by the mitochondrial fusion proteins (Mfn1, Mfn2 and OPA1), and which enables the replenishment of damaged mitochondrial DNA. In the adult heart, mitochondria are relatively static, are constrained in their movement, and are characteristically arranged into 3 distinct subpopulations based on their locality and function (subsarcolemmal, myofibrillar, and perinuclear). Although the mitochondria are arranged differently, emerging data supports a role for the mitochondrial shaping proteins in cardiac health and disease. Interestingly, in the adult heart, it appears that the pleiotropic effects of the mitochondrial fusion proteins, Mfn2 (endoplasmic reticulum-tethering, mitophagy) and OPA1 (cristae remodeling, regulation of apoptosis, and energy production) may play more important roles than their pro-fusion effects. In this review article, we provide an overview of the mitochondrial fusion and fission proteins in the adult heart, and highlight their roles as novel therapeutic targets for treating cardiac disease.
线粒体健康严重依赖于线粒体发生形态变化的能力，这一过程由线粒体塑形蛋白调控。线粒体进行裂变以产生碎片化的离散细胞器，该过程由线粒体裂变蛋白（Drp1、hFIS1、Mff和MiD49/51）介导，是细胞分裂所必需的，并且通过线粒体自噬来清除受损的线粒体。线粒体进行融合以形成细长的相互连接的网络，这一过程由线粒体融合蛋白（Mfn1、Mfn2和OPA1）精心编排，并且能够补充受损的线粒体DNA。在成年心脏中，线粒体相对静止，其运动受到限制，并且根据其位置和功能（肌膜下、肌原纤维和核周）典型地排列成3个不同的亚群。尽管线粒体的排列方式不同，但新出现的数据支持线粒体塑形蛋白在心脏健康和疾病中发挥作用。有趣的是，在成年心脏中，线粒体融合蛋白Mfn2（内质网锚定、线粒体自噬）和OPA1（嵴重塑、细胞凋亡调节和能量产生）的多效性作用似乎比它们的促融合作用发挥着更重要的作用。在这篇综述文章中，我们概述了成年心脏中的线粒体融合和裂变蛋白，并强调它们作为治疗心脏病的新型治疗靶点的作用。
