Selim Laila A, Hassaan Heba
Kasr Al Ainy School of Medicine, Cairo University Children Hospital, Cairo, Egypt.
Adv Exp Med Biol. 2017;1007:129-155. doi: 10.1007/978-3-319-60733-7_8.
"Mitochondria" partially autonomous sophisticated cellular organelle involved in a wide range of crucial cellular functions, well known as the power house of the cell where ATP (adenosine triphosphate) production takes place, that is the cellular source of energy.Mitochondria has its own genome, however proper functioning of the mitochondria is dependent upon the coordinated expression of both nuclear and mitochondrial encoded gene products. Peculiar maternal inheritance of mitochondrial DNA has led the scientists to think about mitochondrial donation as a solution to maternally inherited mitochondriopathy "Three parent baby", raising many ethical and scientific issues, concerns about safety of the procedure, long term outcome and effect of genetic modification are still questionable.Mitochondrial DNA has a higher mutation rate compared to nuclear DNA. Mitochondrial research has revealed a lot about methods of its DNA repair emphasizing the role of nuclear encoded products in this process.Mitochondrial diseases are clinically and genetically diverse, fortunately next generation sequencing (NGS) technologies have made a breakthrough in mitochondrial disorders, the whole mitochondrial genome has been sequenced with more than 250 nuclear encoded genes associated with mitochondrial syndromes identified to date, It unraveled the role of mitochondrial disorders in neurodegenerative disorders. However many pathogenic candidate genes remain uncharacterized even with whole exome sequencing (WES).In this chapter here we handle cases with various neurodegenerative diseases that have been genetically diagnosed thanks to NGS, revealing the role of mitochondrial dysfunction in neurodegeneration, offering a therapeutic target for these handicapping disorders.
线粒体是一种部分自主的复杂细胞器，参与多种关键的细胞功能，是细胞中进行三磷酸腺苷（ATP）生成的场所，即细胞的能量来源，因而被誉为细胞的“动力工厂”。线粒体有自己的基因组，然而其正常功能依赖于核编码和线粒体编码基因产物的协调表达。线粒体DNA独特的母系遗传方式使科学家们考虑将线粒体捐赠作为解决母系遗传线粒体病（“三亲婴儿”）的一种方法，这引发了许多伦理和科学问题，该程序的安全性、长期结果以及基因改造的影响仍然存疑。与核DNA相比，线粒体DNA的突变率更高。线粒体研究揭示了许多关于其DNA修复方法的信息，强调了核编码产物在此过程中的作用。线粒体疾病在临床和遗传方面具有多样性，幸运的是，新一代测序（NGS）技术在线粒体疾病研究方面取得了突破，已对整个线粒体基因组进行了测序，迄今已鉴定出250多个与线粒体综合征相关的核编码基因，揭示了线粒体疾病在神经退行性疾病中的作用。然而，即使采用全外显子组测序（WES），许多致病候选基因仍未得到表征。在本章中，我们处理因NGS技术而得到基因诊断的各种神经退行性疾病病例，揭示线粒体功能障碍在神经退行性变中的作用，为这些致残性疾病提供一个治疗靶点。
