Fig. 7. FANCD2 maintains mitochondrial homeostasis and genome stability by tuning the mitochondrial stress response.

a FANCD2 coordinates nuclear and mitochondrial activities to prevent mitochondrial dysfunction and maintain the mitochondrial stress response (MSR) in check. b Upon mitochondrial stress, FANCD2 relocalizes to CFS and dampens the UBL5-dependent mtUPR, limiting transcription–replication conflicts. c In the absence of FANCD2, mitochondrial dysfunction activates a mitochondrial stress response involving the ATF4 pathway and unrestrained UBL5-dependent CFS gene transcription, leading to transcription-replication collisions and CFS instability.