The Mammalian Longevity-associated Gene Product p66shc Regulates Mitochondrial Metabolism

摘要: Previous studies have determined that mice with a homozygous deletion in the adapter protein p66(shc) an extended life span and cells derived from these exhibit lower levels of reactive oxygen species. Here we demonstrate fraction localizes to mitochondria p66(shc-/-) fibroblasts altered mitochondrial energetics. In particular, despite similar cytochrome content, under basal conditions, consumption spontaneously immortalized mouse embryonic were than similarly maintained wild type cells. Differences particularly evident chemically uncoupled demonstrating reduction both their resting maximal oxidative capacity. We further reconstitution expression increases consumption. The observed defect capacity seen is partially offset by augmented aerobic glycolysis. This metabolic switch manifested exhibiting increase lactate production stricter requirement for extracellular glucose order maintain intracellular ATP levels. addition, using vivo NADH photobleaching technique, metabolism reduced These results regulates suggest may extend repartitioning energy conversion away toward glycolytic pathways.