Mitochondrial sirtuins at the crossroads of energy metabolism and oncogenic transformation

Abstract Nowadays, mitochondrial sirtuins have emerged as potent regulators of acylation of mitochondrial and extramitochondrial proteome with a huge impact on cellular homeostasis. The Sirt3, Sirt4, and Sirt5 activities create a complicated network because their targets frequently overlap, exerting either unidirectional or opposite effects. The direct regulation of numerous mitochondrial metabolic pathways by sirtuins affects the intra- and extramitochondrial balance of intermediate metabolites, which influences gene expression patterns and metabolic reprogramming during oncogenic transformation. This chapter summarizes several aspects of sirtuin biology, including the lipoylation, regulation of the Krebs cycle flux, respiration, and ketogenesis, as well as the iron–sulfur cluster assembly and deoxyribonucleotide synthesis. These processes are commented upon in the context of cancer cell metabolism.