Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster.

ABSTRACT: Sirtuins are an evolutionarily conserved family of NAD⁺-dependent deacylases that control metabolism, stress response, genomic stability, and longevity. Here, we show the sole mitochondrial sirtuin in Drosophila melanogaster, Sirt4, regulates energy homeostasis and longevity. Sirt4 knockout flies have a short lifespan, with increased sensitivity to starvation and decreased fertility and activity. In contrast, flies overexpressing Sirt4 either ubiquitously or specifically in the fat body are long-lived. Despite rapid starvation, Sirt4 knockout flies paradoxically maintain elevated levels of energy reserves, including lipids, glycogen, and trehalose, while fasting, suggesting an inability to properly catabolize stored energy. Metabolomic analysis indica

SUBMITTER: Wood JG 

PROVIDER: S-EPMC5816209 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature