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BNIP3L/NIX-mediated mitophagy protects against ischemic brain injury independent of PARK2
| Content Provider | Scilit |
|---|---|
| Author | Yuan, Yang Zheng, Yanrong Zhang, Xiangnan Chen, Ying Wu, Xiaoli Wu, Jiaying Shen, Zhe Jiang, Lei Wang, Lu Yang, Yuan Luo, Jianhong Qin, Zhenghong Hu, Weiwei Chen, Zhong |
| Copyright Year | 2017 |
| Description | Cerebral ischemia induces massive mitochondrial damage. These damaged mitochondria are cleared, thus attenuating brain injury, by mitophagy. Here, we identified the involvement of BNIP3L/NIX in cerebral ischemia-reperfusion (I-R)-induced mitophagy. Bnip3l knockout $(bnip3l^{−/−}$) impaired mitophagy and aggravated cerebral I-R injury in mice, which can be rescued by BNIP3L overexpression. The rescuing effects of BNIP3L overexpression can be observed in $park2^{−/−}$ mice, which showed mitophagy deficiency after I-R. Interestingly, bnip3l and park2 double-knockout mice showed a synergistic mitophagy deficiency with I-R treatment, which further highlighted the roles of BNIP3L-mediated mitophagy as being independent from PARK2. Further experiments indicated that phosphorylation of BNIP3L serine 81 is critical for BNIP3L-mediated mitophagy. Nonphosphorylatable mutant $BNIP3L^{S81A}$ failed to counteract both mitophagy impairment and neuroprotective effects in $bnip3l^{−/−}$ mice. Our findings offer insights into mitochondrial quality control in ischemic stroke and bring forth the concept that BNIP3L could be a potential therapeutic target for ischemic stroke, beyond its accepted role in reticulocyte maturation. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640199/pdf |
| Ending Page | 1766 |
| Page Count | 13 |
| Starting Page | 1754 |
| ISSN | 15548627 |
| e-ISSN | 15548635 |
| DOI | 10.1080/15548627.2017.1357792 |
| Journal | Autophagy |
| Issue Number | 10 |
| Volume Number | 13 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2017-10-03 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Bnip3l/nix Cerebral Ischemia Mitophagy Park2/parkin Phosphorylation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
