Come and eat: mitochondrial transport guides mitophagy in ischemic neuronal axons
Come and eat: mitochondrial transport guides mitophagy in ischemic neuronal axons
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来吃吧：线粒体运输引导缺血神经元轴突的线粒体自噬
DOI：
10.1080/15548627.2019.1618099
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发表时间：
2019-05
期刊：
影响因子：
13.3
通讯作者：
Zhang Xiangnan
中科院分区：
文献类型：
--
作者：
Zheng Yanrong;Wu Xiaoli;Chen Zhong;Zhang Xiangnan
线粒体自噬是神经元消除多余或受损线粒体的唯一机制。尽管线粒体自噬的重要意义已经在各种神经系统疾病中得到强调，但神经元如何控制轴突线粒体的质量仍然不明确。通过在培养的神经元中使用氧-葡萄糖剥夺和再灌注（OGD-Rep）模型，我们最近的结果清楚地记录了轴突线粒体向神经元体细胞的逆行运输的迅速恢复。此外，通过选择性标记轴突线粒体，我们发现这些轴突线粒体出现在神经元体细胞中，并优先通过自噬体消除。这种从轴突到体细胞的线粒体运动对缺血下神经元的整体线粒体自噬有重要贡献。因为一种锚定蛋白SNPH （Syntaphilin）的强制表达会显著阻断线粒体自噬，并加重线粒体功能障碍和神经元损伤。相反，促进线粒体逆行运动促进神经元自噬并减轻缺血性神经元死亡。综上所述，我们建议在缺血损伤后刺激轴突线粒体的体细胞自噬。这些发现可能为病理状态下神经元如何控制线粒体质量提供进一步的见解，并为治疗神经系统疾病提供新的策略。
ABSTRACT Mitophagy is the sole mechanism for neurons to eliminate superfluous or damaged mitochondria. Although the critical implications of mitophagy have been emphasized in a variety of neurological disorders, it remains ambiguous how neurons control the quality of axonal mitochondria. By employing an oxygen-glucose-deprivation and reperfusion (OGD-Rep) model in cultured neurons, our recent results clearly documented the prompt recovery of retrograde transport of axonal mitochondria to neuronal soma. Moreover, by selectively labeling axonal mitochondria, we found that these axonal mitochondria appear in neuronal soma and are eliminated via autophagosomes in priority. This mitochondrial movement from axon to soma has a critical contribution to overall neuronal mitophagy under ischemia. Because forced expression of an anchoring protein, SNPH (Syntaphilin), significantly blocks mitophagy, and aggravates mitochondrial dysfunction and neuronal injury. Conversely, promoted retrograde mitochondrial movement facilitates neuronal mitophagy and attenuates ischemic neuronal demise. In conclusion, we propose stimulating the somatic autophagy of axonal mitochondria after ischemic insults. These findings may provide further insight into how neurons control the mitochondrial quality in pathological conditions and offer novel strategies to cure neurological disorders.
缺血神经元轴突线粒体的体细胞自噬
DOI：
10.1083/jcb.201804101
发表时间：
2019-04
期刊：
The Journal of Cell Biology
影响因子：
--
作者：
Zheng Yanrong;Zhang Xiangnan;Wu Xiaoli;Jiang Lei;Ahsan Anil;Ma Shijia;Xiao Ziyu;Han Feng;Qin Zheng Hong;Hu Weiwei;Chen Zhong
通讯作者：
Chen Zhong