Open AccessSIRT3 SNPs validation in 640 individuals, functional analyses and new insights into SIRT3 stability
Author(s) -
Christian-Lars Dransfeld,
Hamed Alborzinia,
Stefan Wölfl,
Ulrich Mahlknecht
Publication year - 2010
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo_00000574
Subject(s) - sirt3 , biology , sirtuin , cellular respiration , apoptosis , cell cycle , energy metabolism , microbiology and biotechnology , mitochondrion , genetics , gene , acetylation , endocrinology
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%.