DNA damage invokes mitophagy through a pathway involving Spata18

Mitochondria are vital for cellular energy supply and intracellular signaling after stress. Here, we aimed to investigate how mitochondria respond to acute DNA damage with respect to mitophagy, which is an important mitochondrial quality control process. Our results show that mitophagy increases after DNA damage in primary fibroblasts, murine neurons, and C. elegans neurons. Our results indicate that modulation of mitophagy after DNA damage is independent of the type of DNA damage stimuli used and that the protein Spata18 is an important player in this process. Knockdown of Spata18 suppresses mitophagy, disturbs mitochondrial Ca2+ homeostasis, affects ATP production, and attenuates DNA repair. Importantly, mitophagy after DNA damage is a vital cellular response to maintain mitochondrial functions and DNA repair. mt-keima mice (N=5 per group) were subjected to either sham-treatment or whole body irradiation (6 Gy, delivered at a rate of 0.74 Gy/min), and euthanized 48h later, and cerebellum, cerebrum, heart, licer tissue dissected out for RNA extraction and microarray analysis.