Role of SIRT7 in hepatic lipid metabolism

Excerpt

Sirtuins are evolutionarily conserved enzymes that regulate a wide variety of biological processes, such as aging, genomic stability, tumorigenesis, and metabolism [1]. To date, seven sirtuins have been identified in mammals (SIRT1–SIRT7), which share a highly conserved NAD⁺-binding and catalytic core domain, but have distinct flanking N- and C-terminal domains. The divergent N- and C-termini of sirtuins are responsible for the different functions and subcellular localizations of these enzymes. Although sirtuins were originally described as NAD⁺-dependent histone deacetylases, these enzymes are now known to act not only on histones, but also on numerous transcription factors and enzymes. SIRT1 controls the acetylation of proliferator-activated receptor-γ co-activator 1α (PGC1α), p53, and forkhead box O, among other targets, whereas SIRT3 is a major deacetylase in mitochondria [2, 3]. In addition, a few sirtuins have either weak or undetectable deacetylase activity. For example, SIRT4 is reported to act as an ADP-ribosyltransferase [4], and SIRT5 has both demalonylase and desuccinylase activities [5]. SIRT6 has been shown to deacetylate acetylated lysine 9 of histone H3 (H3K9Ac) and was also recently reported to preferentially hydrolyze long-chain fatty acyl groups on acylated protein targets [6]. …