HIF-1α-BNIP3-mediated mitophagy in tubular cells protects against renal ischemia/reperfusion injury

• DOI: 10.1016/j.redox.2020.101671
• Publication Date: 2020-08-07T07:08:23Z
• Authors: Zong-Jie Fu; Zhi-Yu Wang; Lian Xu; Xiao-Hui Chen; Xiang-Xiao Li; Wei-Tang Liao; Hong-Kun Ma; Meng-Di Jiang; Ting-Ting Xu; Jing Xu; Yan Shen; Bei Song; Ping-Jin Gao; Wei-Qing Han; Wen Zhang
• Keywords: Knockout mouse

In the present study, we hypothesized that hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy plays a protective role in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Mitophagy was evaluated by measuring changes of flux, mitochondria DNA copy number, and mitophagy-related proteins including translocase outer mitochondrial membrane 20 (TOMM20), cytochrome c oxidase IV (COX IV), microtubule-associated protein 1 light chain 3B (LC3B), adaptor nucleoporin p62 HK2 cells, human tubular cell line. Results show HIF-1α knockout significantly attenuated hypoxia/reoxygenation (H/R)-induced mitophagy, aggravated H/R-induced apoptosis, increased production reactive oxygen species (ROS). Similarly, H/R induced increase Bcl-2 19-kDa interacting 3 (BNIP3), downstream regulator HIF-1α. Notably, BNIP3 overexpression reversed inhibitory effect on prevented enhancing apoptosis ROS production. For vivo established HIF-1αflox/flox; cadherin-16-cre mice which specifically knockout. It found inhibited I/R-induced damage. contrast, adenovirus-mediated decreased enhanced damage with I/R injury. summary, our study demonstrated HIF-1α-BNIP3-mediated cells through inhibition