Manolis Antonis S, Manolis Antonis A, Manolis Theodora A, Apostolaki Naomi E, Apostolopoulos Evdoxia J, Melita Helen, Katsiki Niki
First Department of Cardiology, Athens University School of Medicine, Athens, Greece.
Patras University School of Medicine, Patras, Greece.
Med Res Rev. 2021 Jan;41(1):275-313. doi: 10.1002/med.21732. Epub 2020 Sep 21.
Mitochondria provide energy to the cell during aerobic respiration by supplying ~95% of the adenosine triphosphate (ATP) molecules via oxidative phosphorylation. These organelles have various other functions, all carried out by numerous proteins, with the majority of them being encoded by nuclear DNA (nDNA). Mitochondria occupy ~1/3 of the volume of myocardial cells in adults, and function at levels of high-efficiency to promptly meet the energy requirements of the myocardial contractile units. Mitochondria have their own DNA (mtDNA), which contains 37 genes and is maternally inherited. Over the last several years, a variety of functions of these organelles have been discovered and this has led to a growing interest in their involvement in various diseases, including cardiovascular (CV) diseases. Mitochondrial dysfunction relates to the status where mitochondria cannot meet the demands of a cell for ATP and there is an enhanced formation of reactive-oxygen species. This dysfunction may occur as a result of mtDNA and/or nDNA mutations, but also as a response to aging and various disease and environmental stresses, leading to the development of cardiomyopathies and other CV diseases. Designing mitochondria-targeted therapeutic strategies aiming to maintain or restore mitochondrial function has been a great challenge as a result of variable responses according to the etiology of the disorder. There have been several preclinical data on such therapies, but clinical studies are scarce. A major challenge relates to the techniques needed to eclectically deliver the therapeutic agents to cardiac tissues and to damaged mitochondria for successful clinical outcomes. All these issues and progress made over the last several years are herein reviewed.
线粒体在有氧呼吸过程中通过氧化磷酸化提供约95%的三磷酸腺苷（ATP）分子，从而为细胞提供能量。这些细胞器具有多种其他功能，所有功能均由众多蛋白质执行，其中大多数由核DNA（nDNA）编码。线粒体在成年人的心肌细胞中占约1/3的体积，并以高效水平发挥作用，以迅速满足心肌收缩单位的能量需求。线粒体有自己的DNA（mtDNA），包含37个基因，且通过母系遗传。在过去几年中，人们发现了这些细胞器的多种功能，这使得它们在包括心血管（CV）疾病在内的各种疾病中的作用越来越受到关注。线粒体功能障碍是指线粒体无法满足细胞对ATP的需求，且活性氧的形成增加的状态。这种功能障碍可能是由于mtDNA和/或nDNA突变引起的，但也可能是对衰老以及各种疾病和环境应激的反应，从而导致心肌病和其他CV疾病的发生。由于根据疾病病因的不同反应，设计旨在维持或恢复线粒体功能的线粒体靶向治疗策略一直是一项巨大的挑战。关于此类疗法已有一些临床前数据，但临床研究很少。一个主要挑战涉及将治疗药物选择性地递送至心脏组织和受损线粒体以获得成功临床结果所需的技术。本文将对过去几年中所有这些问题及取得的进展进行综述。
