Mitochondrial control of genomic instability in cancer

Mitochondria are well known to participate in multiple aspects of tumor formation and progression. They indeed can alter the susceptibility of cells to engage regulated cell death, regulate pro-survival signal transduction pathways and confer metabolic plasticity that adapts to specific tumor cell demands. Interestingly, a relatively poorly explored aspect of mitochondria in neo-plastic disease is their contribution to the characteristic genomic instability that underlies the evolution of the disease. In this review, we summarize the known mechanisms by which mitochon-drial alterations in cancer tolerate and support the accumulation of DNA mutations which leads to genomic instability. We describe recent studies elucidating mitochondrial responses to DNA damage as well as the direct contribution of mitochondria to favor the accumulation of DNA al-terations. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.