A comprehensive review of Sirtuins: With a major focus on redox homeostasis and metabolism

Sirtuins are Class III protein deacetylases with seven conserved isoforms. In general, Sirtuins are highly activated under cellular stress conditions in which NAD⁺ levels are increased. Nevertheless, regulation of Sirtuins extends far beyond the influences of cellular NAD⁺/NADH ratio and a rapidly expanding body of evidence currently suggests that their expression and catalytic activity are highly kept under control at multiple levels by various factors and processes. Owing to their intrinsic ability to enzymatically target various intracellular proteins, Sirtuins are prominently involved in the regulation of fundamental biological processes including inflammation, metabolism, redox homeostasis, DNA repair and cell proliferation and senescence. In fact, Sirtuins are well established to regulate and reprogram different redox and metabolic pathways under both pathological and physiological conditions. Therefore, alterations in Sirtuin levels can be a pivotal intermediary step in the pathogenesis of several disorders. This review first highlights the mechanisms involved in the regulation of Sirtuins and further summarizes the current findings on the major functions of Sirtuins in cellular redox homeostasis and bioenergetics (glucose and lipid metabolism).