Mitochondrial Energy Metabolism

Mitochondria produce most of the cell’s energy, utilizing the food we eat and the oxygen we breathe. They do so through controlled removal of energy from food intermediates by five multiprotein complexes (I-V). Each of the complexes except complex II is made up of proteins encoded by both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). There is strong overall conservation between homologous proteins of these complexes among primates and, indeed, among mammals. For example, cytochrome oxidase subunit 2, coded by mtDNA, is 96.5% identical between gorilla and human and 71% identical between mouse and human. Examination of the evolution rate of many of the ETC genes has shown that they underwent an acceleration resembling adaptive evolution starting in the stem of the anthropoid primates. Within a species nuclear and mitochondrial genes of each complex coevolve to optimize function, leading to species-specific compatibility. Experiments in which mtDNA from increasingly divergent primate species are placed in a human nuclear background show that, although chimpanzee and gorilla were able to restore oxidative phosphorylation in a human nuclear background, mtDNA from orangutan, Old World and NewWorld monkey species, and lemurs were not, apparently because of defects in cytochrome oxidase assembly. Such rapid evolution in a crucial function may contribute to speciation, and also suggests why this system is so prone to pathogenic mutations of wide-ranging phenotype.