Mitochondria control life and death in eukaryotic cells. Harboring a unique circular genome, a by-product of an ancient endosymbiotic event, mitochondria maintain a specialized and evolutionary divergent protein synthesis machinery, the mitoribosome. Mitoribosome biogenesis depends on elements encoded in both the mitochondrial genome (the RNA components) and the nuclear genome (all ribosomal proteins and assembly factors). Recent cryo-EM structures of mammalian mitoribosomes have illuminated their composition and provided hints regarding their assembly and elusive mitochondrial translation mechanisms. A growing body of literature involves the mitoribosome in inherited primary mitochondrial disorders. Mutations in genes encoding mitoribosomal RNAs, proteins, and assembly factors, impede mitoribosome biogenesis, causing protein synthesis defects that lead to respiratory chain failure and mitochondrial disorders such as encephalo- and cardiomyopathy, deafness, neuropathy, and developmental delays. In this article, we review the current fundamental understanding of mitoribosome assembly and function, and the clinical landscape of mitochondrial disorders driven by mutations in mitoribosome components and assembly factors, to portrait how basic and clinical studies combined help us better understand both mitochondrial biology and medicine.

中文翻译：

---

患病的核糖体

线粒体控制真核细胞的生死。线粒体拥有独特的环状基因组，是古代内共生事件的副产品，它维持着一种专门的、进化的、不同的蛋白质合成机制，即线粒体核糖体。核糖体的生物发生依赖于线粒体基因组（RNA 成分）和核基因组（所有核糖体蛋白和组装因子）中编码的元素。最近哺乳动物线粒体核糖体的冷冻电镜结构阐明了它们的组成，并提供了关于它们的组装和难以捉摸的线粒体翻译机制的提示。越来越多的文献涉及遗传性原发性线粒体疾病中的线粒体核糖体。编码线粒体核糖体 RNA、蛋白质和组装因子的基因突变阻碍了线粒体核糖体的生物发生，导致蛋白质合成缺陷，导致呼吸链衰竭和线粒体疾病，例如脑病和心肌病、耳聋、神经病和发育迟缓。在本文中，我们回顾了当前对线粒体组装和功能的基本认识，以及由线粒体组件和组装因子突变驱动的线粒体疾病的临床前景，以描述基础和临床研究如何结合起来帮助我们更好地了解线粒体生物学和医学.