Advances of SIRT4 in cancer metabolism and therapy.

The Sirtuins family consists of SIRT1-SIRT7, which belong to class III of the histone deacetylases, a family of highly conserved NAD (nicotinamide adenine dinucleotide)-dependent enzymes expressed in the nucleus, cytoplasm, and mitochondria. In addition to having ADP-ribosyltransferase, NAD+-dependent deacetylase, lipoamide, and long-chain deacetylase activities, it can also regulate the function of substrate proteins through ADP-ribosylation, diacylation, and long-chain deacylation. These enzyme activities also confer many critical biological functions on SIRT4, making SIRT4 involved in many mitochondrial energy metabolic processes, such as promoting insulin secretion, participating in the glycolytic process in concert with glycolysis inhibitors, inhibiting glutamate dehydrogenase from regulating glutamine metabolism, and participating in reactions such as DNA damage. Because SIRT4 has such diverse functions, it plays a role in the metabolism and treatment of tumors. Here, we review the progress of SIRT4 research in tumor metabolism and therapy.