phosphocreatine and Li-Fraumeni-Syndrome

There is growing evidence that alterations in metabolism may contribute to tumorigenesis. Here, we report on members of families with the Li-Fraumeni syndrome who carry germline mutations in TP53, the gene encoding the tumor-suppressor protein p53. As compared with family members who are not carriers and with healthy volunteers, family members with these mutations have increased oxidative phosphorylation of skeletal muscle. Basic experimental studies of tissue samples from patients with the Li-Fraumeni syndrome and a mouse model of the syndrome support this in vivo finding of increased mitochondrial function. These results suggest that p53 regulates bioenergetic homeostasis in humans. (Funded by the National Heart, Lung, and Blood Institute and the National Institutes of Health; ClinicalTrials.gov number, NCT00406445.).

Topics: Animals; Case-Control Studies; Disease Models, Animal; Energy Metabolism; Exercise; Female; Genes, p53; Germ-Line Mutation; Heterozygote; Humans; Li-Fraumeni Syndrome; Male; Mice; Mitochondria, Muscle; Muscle, Skeletal; Oxygen Consumption; Phosphocreatine; Pilot Projects; Weight Lifting