Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, 28029, Spain.
Cell Metab. 2012 Sep 5;16(3):378-86. doi: 10.1016/j.cmet.2012.07.015. Epub 2012 Aug 16.
The oxidative phosphorylation system is one of the best-characterized metabolic pathways. In mammals, the protein components and X-ray structures are defined for all complexes except complex I. Here, we show that NDUFA4, formerly considered a constituent of NADH Dehydrogenase (CI), is instead a component of the cytochrome c oxidase (CIV). Deletion of NDUFA4 does not perturb CI. Rather, proteomic, genetic, evolutionary, and biochemical analyses reveal that NDUFA4 plays a role in CIV function and biogenesis. The change in the attribution of the NDUFA4 protein requires renaming of the gene and reconsideration of the structure of CIV. Furthermore, NDUFA4 should be considered a candidate gene for CIV rather than CI deficiencies in humans.
氧化磷酸化系统是研究得最为透彻的代谢途径之一。在哺乳动物中，除了复合物 I 之外，所有复合物的蛋白质成分和 X 射线结构都已确定。在这里，我们表明，先前被认为是 NADH 脱氢酶（CI）组成部分的 NDUFA4 实际上是细胞色素 c 氧化酶（CIV）的组成部分。NDUFA4 的缺失不会干扰 CI。相反，蛋白质组学、遗传学、进化和生化分析表明，NDUFA4 在 CIV 的功能和生物发生中发挥作用。NDUFA4 蛋白归因的变化需要对基因进行重新命名，并重新考虑 CIV 的结构。此外，NDUFA4 应该被视为人类 CIV 而不是 CI 缺乏症的候选基因。
