| First Author | Shi RY | Year | 2014 |
| Journal | CNS Neurosci Ther | Volume | 20 |
| Issue | 12 | Pages | 1045-55 |
| PubMed ID | 25230377 | Mgi Jnum | J:318259 |
| Mgi Id | MGI:6858957 | Doi | 10.1111/cns.12325 |
| Citation | Shi RY, et al. (2014) BNIP3 interacting with LC3 triggers excessive mitophagy in delayed neuronal death in stroke. CNS Neurosci Ther 20(12):1045-55 |
| abstractText | INTRODUCTION: A basal level of mitophagy is essential in mitochondrial quality control in physiological conditions, while excessive mitophagy contributes to cell death in a number of diseases including ischemic stroke. Signals regulating this process remain unknown. BNIP3, a pro-apoptotic BH3-only protein, has been implicated as a regulator of mitophagy. AIMS: Both in vivo and in vitro models of stroke, as well as BNIP3 wild-type and knock out mice were used in this study. RESULTS: We show that BNIP3 and its homologue BNIP3L (NIX) are highly expressed in a "delayed" manner and contribute to delayed neuronal loss following stroke. Deficiency in BNIP3 significantly decreases both neuronal mitophagy and apoptosis but increases nonselective autophagy following ischemic/hypoxic insults. The mitochondria-localized BNIP3 interacts with the autophagosome-localized LC3, suggesting that BNIP3, similar to NIX, functions as a LC3-binding receptor on mitochondria. Although NIX expression is upregulated when BNIP3 is silenced, up-regulation of NIX cannot functionally compensate for the loss of BNIP3 in activating excessive mitophagy. CONCLUSIONS: NIX primarily regulates basal level of mitophagy in physiological conditions, whereas BNIP3 exclusively activates excessive mitophagy leading to cell death. |
