New Hope Biomedical R&D, 23 W. Bridge Street, New Hope, PA 18938, USA.
Biochim Biophys Acta Bioenerg. 2022 Nov 1;1863(8):148595. doi: 10.1016/j.bbabio.2022.148595. Epub 2022 Jul 16.
The cytochrome c oxidase complex, complex VI (CIV), catalyzes the terminal step of the mitochondrial electron transport chain where the reduction of oxygen to water by cytochrome c is coupled to the generation of a protonmotive force that drive the synthesis of ATP. CIV evolution was greatly accelerated in humans and other anthropoid primates and appears to be driven by adaptive selection. However, it is not known if there are significant functional differences between the anthropoid primates CIV, and other mammals. Comparison of the high-resolution structures of bovine CIV, mouse CIV and human CIV shows structural differences that are associated with anthropoid-specific substitutions. Here I examine the possible effects of these substitutions in four CIV peptides that are known to affect proton pumping: the mtDNA-coded subunits I, II and III, and the nuclear-encoded subunit VIa2. I conclude that many of the anthropoid-specific substitutions could be expected to modulate the rate and/or the efficiency of proton pumping. These results are compatible with the previously proposed hypothesis that the accelerated evolution of CIV in anthropoid primates is driven by selection pressure to lower the mitochondrial protonmotive force and thus decrease the rate of superoxide generation by mitochondria.
细胞色素 c 氧化酶复合物，复合物 VI（CIV），催化线粒体电子传递链的最后一步，其中细胞色素 c 将氧还原为水，并与质子动力势的产生偶联，从而驱动 ATP 的合成。CIV 在人类和其他灵长类动物中的进化速度大大加快，似乎是由适应性选择驱动的。然而，目前尚不清楚灵长类动物 CIV 和其他哺乳动物之间是否存在显著的功能差异。牛 CIV、鼠 CIV 和人 CIV 的高分辨率结构比较显示出与灵长类特异性取代相关的结构差异。在这里，我研究了四个已知影响质子泵的 CIV 肽中的这些取代的可能影响：线粒体 DNA 编码的亚基 I、II 和 III 以及核编码的亚基 VIa2。我得出结论，许多灵长类特异性取代可以预期调节质子泵的速度和/或效率。这些结果与之前提出的假设一致，即 CIV 在灵长类动物中的加速进化是由降低线粒体质子动力势的选择压力驱动的，从而降低线粒体中超氧化物的产生速率。
