title: SIRT3 SNPs validation in 640 individuals, functional analyses and new insights into SIRT3 stability.
abstract: Sirtuins are critical players within multiple cellular pathways such as stress response, apoptosis and energy metabolism. They are associated with metabolic and degenerative diseases, the pathogenesis of cancer and are key elements in the regulation of cellular life span. From within the 7 known human sirtuins, SIRT3 recently stepped out of the shadow of SIRT1 showing strong effects on stress response, apoptosis, cell cycle and energy metabolism, mimicking effects of caloric restriction. We have identified two non-synonymous human SIRT3 SNPs and evaluated their impact on SIRT3 activity and stability. We assessed their influence on cellular energy metabolism in relation to SIRT1 and identified SIRT3 to increase cellular respiration by 80% when compared to SIRT1, which increased cellular respiration by only 30%.
authors.affiliation: Saarland University Medical Center, Department of Internal Medicine, Division of Immunotherapy and Gene Therapy, José Carreras Research Center, D-66421 Homburg/Saar, Germany.
authors.forename: Christian-Lars
authors.initials: CL
authors.lastname: Dransfeld
authors.forename: Hamed
authors.initials: H
authors.lastname: Alborzinia
authors.forename: Stefan
authors.initials: S
authors.lastname: Wölfl
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mahlknecht
mesh_terms: D000107:Acetylation; D015374:Biosensing Techniques; D019069:Cell Respiration / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D004795:Enzyme Stability; D005787:Gene Frequency; D005838:Genotype; D006207:Half-Life; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D056566:Sirtuin 3 / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D006657:Histones; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3