Functions of mammalian Sirt4 in cellular metabolism and research progress in human cancer (Review)

Abstract

Sirtuins are mammalian homologs of yeast silent information regulator two (SIRT) and are a highly conserved family of proteins, which act as nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases. The seven sirtuins (SIRT1-7) share a conserved catalytic core domain; however, they have different enzyme activities, biological functions, and subcellular localizations. Among them, mitochondrial SIRT4 possesses ADP-ribosyltransferase, NAD+-dependent deacetylase, lipoamidase, and long-chain deacylase activities and can modulate the function of substrate proteins via ADP-ribosylation, delipoylation, deacetylation and long-chain deacylation. SIRT4 has been shown to play a crucial role in insulin secretion, fatty acid oxidation, amino acid metabolism, ATP homeostasis, apoptosis, neurodegenera- tion, and cardiovascular diseases. In addition, recent studies have demonstrated that SIRT4 acts as a tumor suppressor. Here, the present review summarizes the enzymatic activi- ties and biological functions of SIRT4, as well as its roles in cellular metabolism and human cancer, which are described in the current literature.