| First Author | Zhao Q | Year | 2022 |
| Journal | Cell Death Dis | Volume | 13 |
| Issue | 11 | Pages | 976 |
| PubMed ID | 36402748 | Mgi Jnum | J:346882 |
| Mgi Id | MGI:7387294 | Doi | 10.1038/s41419-022-05413-4 |
| Citation | Zhao Q, et al. (2022) BNIP3-dependent mitophagy safeguards ESC genomic integrity via preventing oxidative stress-induced DNA damage and protecting homologous recombination. Cell Death Dis 13(11):976 |
| abstractText | 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 of AMPK in Bnip3(-/-) ESCs under X-ray stress remarkably decreased the mutation load. In addition, enhancement of BNIP3-dependent mitophagy during reprogramming markedly decreased mutation accumulation in established iPSCs. In conclusion, we demonstrated a novel pathway in which BNIP3-dependent mitophagy safeguards ESC genomic stability, and that could potentially be targeted to improve pluripotent stem cell genomic integrity for regenerative medicine. |
