The mammalian sirtuin family consists of seven proteins, three of which (SIRT3, SIRT4, and SIRT5) localise specifically within mitochondria and preserve mitochondrial function and homeostasis. Mitochondrial sirtuins are involved in diverse functions such as deacetylation, ADP-ribosylation, demalonylation and desuccinylation, thus affecting various aspects of cell fate. Intriguingly, mitochondrial sirtuins are able to manage these delicate processes with accuracy mediated by crosstalk between the nucleus and mitochondria. Previous studies have provided ample information about their substrates and targets, whereas less is known about their role in cancer and stem cells. Here, we review and discuss recent advances in our understanding of the structural and functional properties of mitochondrial sirtuins, including their targets in cancer and stem cells. These advances could help to improve the understanding of their interplay with signalling cascades and pathways, leading to new avenues for developing novel drugs for sirtuin-related disease treatments. We also highlight the complex network of mitochondrial sirtuins in cancer and stem cells, which may be important in deciphering the molecular mechanism for their activation and inhibition.
Keywords: SIRT3; SIRT4; SIRT5; cancer; mitochondria; sirtuins; stem cells.
© 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.