**5. Mitonuclear communication regulates apoptosis, DNA repair, and aging**

The mechanisms by which nuclear DNA damage signaling causes the mitochondrial dysfunctions that accelerate aging and aging-related diseases including cancer have been investigated in a review [134]. This process can be referred to as "mitonuclear communication" [135], suggesting that DNA repair systems are integrated into the mitochondrial functions. Given that α proteobacteria are the putative ancestors of the mitochondria [136], they need to take care of the nuclear DNAs that contain almost all (99%) of their essential protein-encoding genes [9]. Thus, the mitochondria might have developed a nuclear genome monitoring system, especially when DNA damage is induced. Several TCA cycles or metabolic enzymes functions as tumor suppressors [59, 64, 137], suggesting that mitochondrial dysfunction may lead to cancerous states.
