Mitochondrial DNA Mutations as a Factor in the Heritability of Atherosclerosis and Other Diseases.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Alexander N Orekhov, Nikolay A Orekhov, Vasily N Sukhorukov, Victoria A Khotina, Tatiana I Kovianova, Igor A Sobenin
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Abstract

This review discusses the possibility of inheritance of some diseases through mutations in mitochondrial DNA. These are examples of many mitochondrial diseases that can be caused by mutations in mitochondrial DNA. Symptoms and severity can vary widely depending on the specific mutation and affected tissues. An association between certain mutations in the mitochondrial genome and cancer was reported. In other studies of 2-4 generations in each family, we found that mitochondrial mutations associated with atherosclerosis are inherited. This may at least partially explain the inheritance of predisposition to atherosclerotic disease by maternal line. Furthermore, to prove the important role of mitochondrial mutations in the development of atherosclerotic manifestations at the cellular level, we developed a technique for editing the mitochondrial genome. A recent article described how one of the pro-atherogenic mutations, namely m.15059G>A, was eliminated from such monocyte-derived cells using the technique we developed. Elimination of this mutation resulted in the restoration to normal levels of initially defective mitophagy and impaired inflammatory response. These data strongly suggest that mitochondrial mutations are closely associated with the development of atherosclerotic lesions. Considering that they are inherited, it can be assumed that, at least partly, the genetic predisposition to atherosclerotic diseases is transmitted from mother to offspring. Thus, despite the small size of mitochondrial DNA, its mutations may play a role in the pathogenesis of diseases. Further study of their role will make it possible to consider mitochondrial mutations as promising diagnostic markers and disorders caused by mutations as pharmacological targets.

线粒体DNA突变是动脉粥样硬化和其他疾病遗传的一个因素。
本文综述了一些疾病通过线粒体DNA突变遗传的可能性。这些是许多线粒体疾病的例子,这些疾病可能是由线粒体DNA突变引起的。根据特定的突变和受影响的组织,症状和严重程度可能有很大差异。据报道,线粒体基因组的某些突变与癌症之间存在关联。在每个家族2-4代人的其他研究中,我们发现与动脉粥样硬化相关的线粒体突变是遗传的。这至少可以部分解释动脉粥样硬化性疾病的母系遗传倾向。此外,为了证明线粒体突变在细胞水平动脉粥样硬化表现发展中的重要作用,我们开发了一种编辑线粒体基因组的技术。最近的一篇文章描述了如何使用我们开发的技术从这种单核细胞来源的细胞中消除一种促动脉粥样硬化突变,即m.15059G>A。消除这种突变导致恢复到正常水平的最初有缺陷的有丝分裂和受损的炎症反应。这些数据有力地表明,线粒体突变与动脉粥样硬化病变的发展密切相关。考虑到它们是遗传的,可以假设,至少部分地,动脉粥样硬化疾病的遗传易感性是由母亲传给后代的。因此,尽管线粒体DNA的体积很小,但其突变可能在疾病的发病机制中发挥作用。对其作用的进一步研究将有可能将线粒体突变作为有前途的诊断标记物,并将突变引起的疾病作为药理学靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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