Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome.
Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome.
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DOI：
10.1042/bcj20190767
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发表时间：
2020-11-13
期刊：
影响因子：
--
通讯作者：
Stroud DA
中科院分区：
文献类型：
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作者：
Hock DH;Robinson DRL;Stroud DA
线粒体通过氧化磷酸化(OXPHOS)产生几乎所有真核细胞所需的大部分能量，氧化磷酸化发生在呼吸链和F1-F0 ATPase的四个复合体上。线粒体疾病是一组影响OXPHOS的异质性疾病，直接通过编码OXPHOS复合体亚单位的基因突变，或间接通过编码支持这一过程的蛋白质的基因突变。这些包括促进OXPHOS复合体的组装、亚基的翻译后修饰、辅因子的插入或亚基合成的蛋白质。后者对人类线粒体DNA编码的所有13种蛋白质都是重要的，这些蛋白质是在线粒体核糖体上合成的。这五个OXPHOS复合体和线粒体核糖体总共由160多个亚基组成，更多的蛋白质支持它们的生物发生。编码这些蛋白质的核基因和线粒体基因的突变已被报道导致线粒体疾病，许多突变导致复杂组装缺陷，组装缺陷的严重程度反映了疾病的严重程度。这篇综述旨在作为支持我们对OXPHOS复合体和核糖体组装的知识的临床和基础研究与线粒体疾病中这一过程的功能障碍之间的接口。
Mitochondria produce the bulk of the energy used by almost all eukaryotic cells through oxidative phosphorylation (OXPHOS) which occurs on the four complexes of the respiratory chain and the F1–F0 ATPase. Mitochondrial diseases are a heterogenous group of conditions affecting OXPHOS, either directly through mutation of genes encoding subunits of OXPHOS complexes, or indirectly through mutations in genes encoding proteins supporting this process. These include proteins that promote assembly of the OXPHOS complexes, the post-translational modification of subunits, insertion of cofactors or indeed subunit synthesis. The latter is important for all 13 of the proteins encoded by human mitochondrial DNA, which are synthesised on mitochondrial ribosomes. Together the five OXPHOS complexes and the mitochondrial ribosome are comprised of more than 160 subunits and many more proteins support their biogenesis. Mutations in both nuclear and mitochondrial genes encoding these proteins have been reported to cause mitochondrial disease, many leading to defective complex assembly with the severity of the assembly defect reflecting the severity of the disease. This review aims to act as an interface between the clinical and basic research underpinning our knowledge of OXPHOS complex and ribosome assembly, and the dysfunction of this process in mitochondrial disease.