BNIP3 (BCL2 interacting protein 3) regulates pluripotency by modulating mitochondrial homeostasis via mitophagy.

Kun Liu, Qian Zhao, Hongyan Sun, Lei Liu, Chaoqun Wang, Zheng Li, Youqing Xu, Liang Wang, Lin Zhang, Honghai Zhang, Quan Chen, Tongbiao Zhao

Cell death & disease 2022 Apr 11

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Autophagy-mediated mitochondrial degradation plays pivotal roles in both the acquisition and maintenance of pluripotency, but the molecular mechanisms that link autophagy-mediated mitochondrial homeostasis to pluripotency regulation are unclear. Here, we identified that the mitophagy receptor BNIP3 regulates pluripotency. In mouse ESCs, depletion of BNIP3 caused accumulation of aberrant mitochondria accompanied by decreased mitochondrial membrane potential, increased production of reactive oxygen species (ROS), and reduced ATP generation, which led to compromised self-renewal and differentiation. Impairment of mitophagy by knockdown of BNIP3 inhibited mitochondrial clearance during pluripotency induction, resulting in decreased reprogramming efficiency. These defects were rescued by reacquisition of wild-type but not LIR-deficient BNIP3 expression. Taken together, our findings highlight a critical role of BNIP3-mediated mitophagy in the induction and maintenance of pluripotency. © 2022. The Author(s).

Citation

Kun Liu, Qian Zhao, Hongyan Sun, Lei Liu, Chaoqun Wang, Zheng Li, Youqing Xu, Liang Wang, Lin Zhang, Honghai Zhang, Quan Chen, Tongbiao Zhao. BNIP3 (BCL2 interacting protein 3) regulates pluripotency by modulating mitochondrial homeostasis via mitophagy. Cell death & disease. 2022 Apr 11;13(4):334