Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential.

The past few decades have witnessed a furious attention of scientific community toward identifying novel molecular factors and targets that could be exploited for drug development for cancer management. One such factor is the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases. The role of SIRTs in cancer is extremely complex, with dichotomous functions depending on cell contexts. Mammalian SIRTs (SIRT1-7) differ in their cellular localization and biologic functions. Among these, SIRT -3, -4, and -5 are located in the mitochondria and are being carefully investigated. These mitochondrial SIRTs (mtSIRT) regulate multiple cellular and physiologic processes, including cell cycle, gene expression, cell viability, stress response, metabolism, and energy homeostasis. Recent research suggests that mtSIRTs influence tumors by regulating the metabolic state of the cell. Although the research on the role of mtSIRTs in cancer is still in its infancy, studies have suggested tumor suppressor as well as tumor promoter roles for them. This review is focused on discussing up-to-date information about the roles and functional relevance of mtSIRTs (SIRT -3, -4, -5) in cancers. We have also provided a critical discussion and our perspective on their dual roles, as tumor promoter versus tumor suppressor, in cancer. Cancer Res; 76(9); 2500-6. ©2016 AACR.