Bnip3, also known as BCL2/adenovirus E1B interacting protein 3, is a protein related to the BH3-only family. It has a dual role in both cell death and autophagy, especially mitophagy. Bnip3 is regulated by hypoxia and is involved in the HIF1A-mediated hypoxia signaling pathway [1,2,3]. It is of great biological importance as it participates in maintaining mitochondrial homeostasis and is implicated in multiple disease-related processes.

In various disease models, gene knockout studies have revealed its significance. In contrast-induced acute kidney injury (CI-AKI) mouse models, Bnip3 deficiency exacerbated apoptosis and renal injury, suggesting that Bnip3-mediated mitophagy has a protective function [1]. In renal ischemia-reperfusion injury mouse models, Bnip3 knockout worsened renal injury, as it reduced mitophagy, led to damaged mitochondrial accumulation, increased reactive oxygen species production, and enhanced cell death and inflammation [4]. Also, overexpression of Bnip3 in the heart prevented the improvement in cardiac function caused by semaglutide in a doxorubicin-induced cardiotoxicity model, indicating its role in mitochondrial and cardiac dysfunction [5].

In conclusion, Bnip3 is a crucial regulator of cell fate, with its function in mitophagy being essential for maintaining mitochondrial quality control and cell survival. Gene knockout mouse models have significantly contributed to understanding its role in diseases such as CI-AKI, renal ischemia-reperfusion injury, and doxorubicin-induced cardiotoxicity, providing insights into potential therapeutic strategies for these conditions.

References:

1. Lin, Qisheng, Li, Shu, Jiang, Na, Lu, Renhua, Ni, Zhaohui. 2020. Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy. In Autophagy, 17, 2975-2990. doi:10.1080/15548627.2020.1848971. https://pubmed.ncbi.nlm.nih.gov/33345685/

2. Zhang, J, Ney, P A. 2009. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. In Cell death and differentiation, 16, 939-46. doi:10.1038/cdd.2009.16. https://pubmed.ncbi.nlm.nih.gov/19229244/

3. Zhang, Yanan, Liu, Dawei, Hu, Haijuan, Xie, Ruiqin, Cui, Wei. 2019. HIF-1α/BNIP3 signaling pathway-induced-autophagy plays protective role during myocardial ischemia-reperfusion injury. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 120, 109464. doi:10.1016/j.biopha.2019.109464. https://pubmed.ncbi.nlm.nih.gov/31590128/

4. Tang, Chengyuan, Han, Hailong, Liu, Zhiwen, Yin, Xiao-Ming, Dong, Zheng. 2019. Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury. In Cell death & disease, 10, 677. doi:10.1038/s41419-019-1899-0. https://pubmed.ncbi.nlm.nih.gov/31515472/

5. Li, Xiaoping, Luo, Wenbin, Tang, Yang, Guo, Li, Zeng, Chunyu. 2024. Semaglutide attenuates doxorubicin-induced cardiotoxicity by ameliorating BNIP3-Mediated mitochondrial dysfunction. In Redox biology, 72, 103129. doi:10.1016/j.redox.2024.103129. https://pubmed.ncbi.nlm.nih.gov/38574433/