BNIP3-dependent mitophagy safeguards ESC genomic integrity via preventing oxidative stress-induced DNA damage and protecting homologous recombination.

ABSTRACT: Embryonic stem cells (ESCs) have a significantly lower mutation load compared to somatic cells, but the mechanisms that guard genomic integrity in ESCs remain largely unknown. Here we show that BNIP3-dependent mitophagy protects genomic integrity in mouse ESCs. Deletion of Bnip3 increases cellular reactive oxygen species (ROS) and decreases ATP generation. Increased ROS in Bnip3^-/- ESCs compromised self-renewal and were partially rescued by either NAC treatment or p53 depletion. The decreased cellular ATP in Bnip3^-/- ESCs induced AMPK activation and deteriorated homologous recombination, leading to elevated mutation load during long-term propagation. Whereas activation of AMPK in X-ray-treated Bnip3^+/+ ESCs dramatically ascended mutation rates, inactivation

SUBMITTER: Zhao Q 

PROVIDER: S-EPMC9675825 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature