BNIP3 Interacting with LC3 Triggers Excessive Mitophagy in Delayed Neuronal Death in Stroke. (17th September 2014)

• Record Type: Journal Article
• Authors: Shi, Ruo‐Yang; Zhu, Sheng‐Hua; Li, Victor; Gibson, Spencer B.; Xu, Xing‐Shun; Kong, Ji‐Ming
• Is Part Of: CNS neuroscience & therapeutics. Volume 20:Number 12(2014)
• Page Start: 1045
• Page End: 1055
• Publication Date: 2014-09-17
• Subjects: Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.12325
• Languages: English
• ISSNs: 1755-5930

Abstract

<abstract abstract-type="main" id="cns12325-abs-0001"> <title>Summary</title> <sec id="cns12325-sec-0001" sec-type="section"> <title>Introduction</title> <p>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.</p> </sec> <sec id="cns12325-sec-0002" sec-type="section"> <title>Aims</title> <p>Both <italic>in vivo</italic> and <italic>in vitro</italic> models of stroke, as well as BNIP3 wild‐type and knock out mice were used in this study.</p> </sec> <sec id="cns12325-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="cns12325-sec-0004" sec-type="section"> <title>Conclusions</title> <p>NIX primarily regulates basal level of mitophagy in physiological conditions, whereas BNIP3 exclusively activates excessive mitophagy leading to cell death.</p> </sec> </abstract>