Samangouei Parisa, Crespo-Avilan Gustavo E, Cabrera-Fuentes Hector, Hernández-Reséndiz Sauri, Ismail Nur Izzah, Katwadi Khairunnisa Binte, Boisvert William A, Hausenloy Derek J
Hatter Cardiovascular Institute, University College London, UK.
Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore.
Cond Med. 2018 Aug;1(5):239-246.
Acute myocardial infarction (AMI) and the heart failure (HF) that often follows are among the leading causes of death and disability worldwide. As such novel therapies are needed to reduce myocardial infarct (MI) size, and preserve left ventricular (LV) systolic function in order to reduce the propensity for HF following AMI. Mitochondria are dynamic organelles that can undergo morphological changes by two opposing processes, mitochondrial fusion and fission. Changes in mitochondrial morphology and turnover are a vital part of maintaining mitochondrial health, DNA stability, energy production, calcium homeostasis, cellular division, and differentiation, and disturbances in the balance of fusion and fission can predispose to mitochondrial dysfunction and cell death. Changes in mitochondrial morphology are governed by mitochondrial fusion proteins (Mfn1, Mfn2 and OPA1) and mitochondrial fission proteins (Drp1, hFis1, and Mff). Recent experimental data suggest that mitochondria undergo fission during acute ischemia/reperfusion injury (IRI), generating fragmented dysfunctional mitochondrial and predisposing to cell death. We and others have shown that genetic and pharmacological inhibition of the mitochondrial fission protein Drp1 can protect cardiomyocytes from acute IRI and reduce MI size. Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and mitochondrial dynamics proteins of 51 kDa (MiD51), have been recently described, which have been shown to mediating mitochondrial fission by targeting Drp1 to the mitochondrial surface. In this review article, we provide an overview of MiD49 and MiD51, and highlight their potential as novel therapeutic targets for treating cardiovascular diseases such as AMI, anthracycline cardiomyopathy, and pulmonary arterial hypertension.
急性心肌梗死（AMI）以及随之而来的心力衰竭（HF）是全球范围内死亡和残疾的主要原因之一。因此，需要新的治疗方法来减小心肌梗死（MI）面积，并保留左心室（LV）收缩功能，以降低AMI后发生HF的倾向。线粒体是动态细胞器，可通过线粒体融合和裂变这两个相反的过程发生形态变化。线粒体形态和更新的变化是维持线粒体健康、DNA稳定性、能量产生、钙稳态、细胞分裂和分化的重要组成部分，融合与裂变平衡的紊乱会导致线粒体功能障碍和细胞死亡。线粒体形态的变化受线粒体融合蛋白（Mfn1、Mfn2和OPA1）和线粒体裂变蛋白（Drp1、hFis1和Mff）的调控。最近的实验数据表明，在急性缺血/再灌注损伤（IRI）期间线粒体发生裂变，产生功能失调的碎片化线粒体并导致细胞死亡。我们和其他人已经表明，对线粒体裂变蛋白Drp1进行基因和药理学抑制可以保护心肌细胞免受急性IRI的影响，并减小MI面积。最近描述了线粒体裂变机制的新成分，即49 kDa的线粒体动力学蛋白（MiD49）和51 kDa的线粒体动力学蛋白（MiD51），它们已被证明通过将Drp1靶向线粒体表面来介导线粒体裂变。在这篇综述文章中，我们概述了MiD49和MiD51，并强调了它们作为治疗心血管疾病（如AMI、蒽环类心肌病和肺动脉高压）的新治疗靶点的潜力。
