Exceptional longevity and exceptionally high metabolic rates in anthropoid primates are linked to a major modification of the ubiquinone reduction site of cytochrome b.
The maximal lifespan of Anthropoid primates (monkeys, apes and humans) exceed the lifespan of most other mammals of equal body mass. Unexpectedly, their exceptional longevity is associated with exceptionally high metabolic rates, in apparent contradiction to the Free Radical Theory of Aging. It was therefore suggested that in anthropoid primates (and several other taxa of mammals and birds) the mitochondrial electron transport complexes evolved to modify the relationship between basal electron transport and superoxide generation to allow for the evolution of exceptional longevity. Cytochrome b, the core protein of the bc1 complex is a major source of superoxide. The amino-acid sequence of cytochrome b evolved much faster in anthropoid than in prosimian primates, and most other mammals, resulting in a large change in the amino-acids composition of the protein. As a result of these changes cytochrome b in anthropoid primates is significantly less hydrophobic and contains more polar residues than other primates and most other mammals. Most of these changes are clustered around the reduction site of uboiquinone. In particular a key positively charged residue, arginine 313, that interacts with propionate D of heme bH, and thus raises its redox potential, is substituted in anthropoid primates with the neutral residue glutamine, most likely resulting in a lower redox potential of heme bH and faster reduction of ubiquinone at high proton motive force. It is suggested that these changes contribute to the observed increased rates of basal metabolism and reduce the rates of superoxide production, thus allowing for increased lifespan.
New Hope Biomedical R&D, 23 W. Bridge Street, New Hope, PA, 18938, USA, rotteh@hotmail.com.
Hagai
H
Rottenberg
D000367:Age Factors; D000818:Animals; D001481:Basal Metabolism; D045303:Cytochromes b / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008136:Longevity; D008322:Mammals; D008928:Mitochondria / Q000378:metabolism*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011323:Primates; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism*
D017382:Reactive Oxygen Species; D014451:Ubiquinone; D045303:Cytochromes b