The mitochondrial respiratory chain (MRC) is comprised of ∼92 nuclear and mitochondrial DNA-encoded protein subunits that are organized into five different multi-subunit respiratory complexes. These complexes produce 90% of the ATP required for cell sustenance. Specific sets of subunits are assembled in a modular or non-modular fashion to construct the MRC complexes. The complete assembly process is gradually chaperoned by a myriad of assembly factors that must coordinate with several other prosthetic groups to reach maturity, makingthe entire processextensively complicated. Further, the individual respiratory complexes can be integrated intovarious giant super-complexes whose functional roles have yet to be explored. Mutations in the MRC subunits and in the related assembly factors often give rise to defects in the proper assembly of the respiratory chain, which then manifests as a group of disorders called mitochondrial diseases, the most common inborn errors of metabolism. This review summarizes the current understanding of the biogenesis of individual MRC complexes and super-complexes, and explores how mutations in the different subunits and assembly factors contribute to mitochondrial disease pathology.

中文翻译：

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线粒体呼吸链组装的分子机制及其与线粒体疾病的关系

线粒体呼吸链 (MRC) 由约 92 个核和线粒体 DNA 编码的蛋白质亚基组成，这些亚基被组织成五个不同的多亚基呼吸复合物。这些复合物产生细胞维持所需的 90% 的 ATP。特定的亚基组以模块化或非模块化方式组装以构建 MRC 复合体。完整的组装过程逐渐受到无数组装因素的陪伴，这些因素必须与其他几个假肢组协调才能达到成熟，使整个过程变得极其复杂。此外，单个呼吸复合体可以整合成各种巨大的超级复合体，其功能作用尚待探索。MRC 亚基和相关组装因子的突变通常会导致呼吸链正确组装的缺陷，然后表现为一组称为线粒体疾病的疾病，这是最常见的先天性代谢缺陷。本综述总结了目前对单个 MRC 复合物和超复合物的生物发生的理解，并探讨了不同亚基和组装因子中的突变如何导致线粒体疾病病理学。