Figure 5. MDF in FA cells is dependent on ROS and impaired mitophagy.

Defects in DNA damage response FA genes result in OS which, in turn, damages mitochondrial parameters and eventually leads to MDF. In healthy cells (FAcor) dysfunctional mitochondria are removed from the intact mitochondrial reticular by mitophagy. Mitochondrial fission is necessary for the induction of mitophagy under mild OS and helps to segregate normal and damaged mitochondria. Activation of AMPK and mTOR signal cells to rapid mitochondrial fragmentation by triggering DRP1. In unhealthy condition, such as in FA, cells can not remove dysfunctional mitochondria because mitophagy is impaired. Therefore, accumulation of damaged mitochondria takes places leading to physiological consequences that impact overall FA phenotype.