Mitochondrial diseases are extremely heterogeneous genetic conditions characterized by faulty oxidative phosphorylation (OxPhos). OxPhos deficiency can be the result of mutation in mtDNA genes, encoding either proteins (13 subunits of the mitochondrial complexes I, III, IV and V) or the tRNA and rRNA components of the in situ mtDNA translation. The remaining mitochondrial disease genes are in the nucleus, encoding proteins with a huge variety of functions, from structural subunits of the mitochondrial complexes, to factors involved in their formation and regulation, components of the mtDNA replication and expression machinery, biosynthetic enzymes for the biosynthesis or incorporation of prosthetic groups, components of the mitochondrial quality control and proteostasis, enzymes involved in the clearance of toxic compounds, factors involved in the formation of the lipid milieu, etc. These different functions represent potential targets for "general" therapeutic interventions, as they may be adapted to a number of different mitochondrial conditions. This is in contrast with "tailored", personalized therapeutic approaches, such as gene therapy, cell therapy and organ replacement, that can be useful only for individual conditions. This review will present the most recent concepts emerged from preclinical work and the attempts to translate them into the clinics. The common notion that mitochondrial disorders have no cure is currently challenged by a massive effort of scientists and clinicians, and we do expect that thanks to this intensive investigation work, tangible results for the development of strategies amenable to the treatment of patients with these tremendously difficult conditions are not so far away.

中文翻译：

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对抗线粒体疾病的策略。

线粒体疾病是异常异质的遗传疾病，其特征是氧化磷酸化作用（OxPhos）错误。OxPhos缺乏症可能是编码蛋白质（线粒体复合物I，III，IV和V的13个亚基）或原位mtDNA翻译的tRNA和rRNA组件的mtDNA基因突变的结果。其余的线粒体疾病基因位于细胞核中，编码具有多种功能的蛋白质，从线粒体复合物的结构亚基到涉及其形成和调控的因子，mtDNA复制和表达机制的成分，用于生物合成的生物合成酶或掺入修复基团，线粒体质量控制成分和蛋白稳态，参与清除有毒化合物的酶，这些不同的功能代表“一般”治疗干预的潜在目标，因为它们可以适应许多不同的线粒体疾病。这与“量身定制”的个性化治疗方法（例如基因治疗，细胞治疗和器官置换）相反，后者仅对个别情况有用。这篇综述将介绍临床前工作中出现的最新概念以及将其转化为临床的尝试。线粒体疾病无法治愈的普遍观念目前正受到科学家和临床医生的巨大努力的挑战，我们希望通过这项深入的研究工作，