Sirtuins play an important role in signalling pathways associated with various metabolic regulations. They possess mono-ADP-ribosyltransferase or deacylase activity like demalonylase, deacetylase, depalmitoylase, demyristoylase and desuccinylase activity. Sirtuins are histone deacetylases which depends upon nicotinamide adenine dinucleotide (NAD) that deacetylate lysine residues. There are a total of seven human sirtuins that have been identified namely, SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7. The subcellular location of mammalian sirtuins, SIRT1, SIRT6, and SIRT7 are in the nucleus; SIRT3, SIRT4, and SIRT5 are in mitochondria, and SIRT2 is in cytoplasm. Structurally sirtuins contains a N-terminal, a C-terminal and a Zn+ binding domain. The sirtuin family has been found to be crucial for maintaining lipid and glucose homeostasis, and also for regulating insulin secretion and sensitivity, DNA repair pathways, neurogenesis, inflammation, and ageing. Based on the literature, sirtuins are overexpressed and play an important role in tumorigenicity in various types of cancer such as non-small cell lung cancer, colorectal cancer, etc. In this review, we have discussed about the different types of human sirtuins along with their structural and functional features. We have also discussed about the various natural and synthetic regulators of sirtuin activities like resveratrol. Our overall study shows that the correct regulation of sirtuins can be a good target for preventing and treating various diseases for improving the human lifespan. To investigate the true therapeutic potential of sirtuin proteins and their efficacy in a variety of pathological diseases, a better knowledge of the link between the structure and function of sirtuin proteins would be necessary.

Mitochondrial permeability transition pore (mPTP) is a channel that opens at the inner mitochondrial membrane under conditions of stress. Sirtuin 3 (Sirt3) is a mitochondrial deacetylase known to play a major role in stress resistance and a regulatory role in cell death. This systematic review aims to elucidate the role of Sirt3 in mPTP inhibition. Electronic databases, including PubMed, EMBASE, Web of Science and Cochrane Library were searched up to May 2020. Original studies that investigated the relationship between Sirt3 and mPTP were included. Two reviewers independently extracted data on study characteristics, methods and outcomes. A total of 194 articles were found. Twenty-nine articles, which met criteria were included in the systematic review. Twenty-three studies provided evidence of the inhibitory effect of Sirt3 on the mPTP aperture. This review summarizes up-to-date evidence of the protective and inhibitory role of Sirt3 through deacetylating Cyclophilin D (CypD) on the mPTP aperture. Furthermore, we discuss the implications of this effect in disease.