Mitochondrial sirtuins: Emerging roles in metabolic regulations, energy homeostasis and diseases

•Paper explores the localization, enzymatic activities and regulation of mitochondrial sirtuins.•Paper updates recent knowledge on the role of mitochondrial sirtuins in regulation of metabolism and energy homeostasis.•Paper explains the role of mitochondrial sirtuins in oxidative stress, apoptosis, and mitochondrial biogenesis.•Paper describes the role of sirtuins in the regulation of metabolic diseases resulting from mitochondrial impairments.•Paper explores therapeutic applications of targeting mitochondrial sirtuins by bioactive compounds in human diseases.

The energy production and metabolic homeostasis are well-orchestrated networks of carbohydrate, lipid and protein metabolism. These metabolic pathways are integrated by a key cytoplasmic organelle, the mitochondria, leading to production of many metabolic intermediates and harvest cellular energy in the form of ATP. Sirtuins are a highly conserved family of proteins that mediate cellular physiology and energy demands in response to metabolic inputs. Mitochondria inhabit three main types of sirtuins classified as Sirt3, Sirt4 and Sirt5. These sirtuins regulate mitochondrial metabolic functions mainly through controlling post-translational modifications of mitochondrial protein. However, the biological mechanism involved in controlling mitochondrial metabolic functions is not well understood at this stage. In this review the current knowledge on how mitochondrial sirtuins govern mitochondrial functions including energy production, metabolism, biogenesis and their involvement in different metabolic pathways are discussed. The identifications of potential pharmacological targets of sirtuins in the mitochondria and the bioactive compounds that target mitochondrial sirtuins will increase our understanding on regulation of mitochondrial metabolism in normal and disease state.