The Mammalian-Specific Protein Armcx1 Regulates Mitochondrial Transport during Axon Regeneration.

The Mammalian-Specific Protein Armcx1 Regulates Mitochondrial Transport during Axon Regeneration.
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DOI:
10.1016/j.neuron.2016.10.060
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发表时间:
2016-12-21
期刊:
影响因子:
16.2
通讯作者:
He Z
He Z
中科院分区:
医学1区
文献类型:
--
作者:
Cartoni R;Norsworthy MW;Bei F;Wang C;Li S;Zhang Y;Gabel CV;Schwarz TL;He Z

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线粒体运输对神经元和轴突生理至关重要。然而,它是否以及如何影响神经元损伤反应,如神经元存活和轴突再生,在很大程度上仍然未知。在已建立的具有强大轴突再生的小鼠模型中,我们发现Armcx1,一种哺乳动物特异性基因,编码线粒体定位蛋白,在这种高再生条件下,在轴突切除后上调。Armcx1过表达增强成人视网膜神经节细胞(RGCs)的线粒体运输。重要的是,Armcx1还促进损伤后神经元存活和轴突再生,这些作用取决于其线粒体定位。此外,在高再生能力模型中,Armcx1敲低会破坏神经元存活和轴突再生,进一步支持了Armcx1在调节成人中枢神经系统(CNS)神经元损伤反应中的关键作用。我们的研究结果表明,在神经元修复过程中,Armcx1控制着线粒体运输。
Mitochondrial transport is crucial for neuronal and axonal physiology. However, whether and how it impacts neuronal injury responses, such as neuronal survival and axon regeneration, remain largely unknown. In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is up-regulated after axotomy in this high regeneration condition. Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs). Importantly, Armcx1 also promotes both neuronal survival and axon regeneration after injury, and these effects depend on its mitochondrial localization. Furthermore, Armcx1 knockdown undermines both neuronal survival and axon regeneration in the high regenerative capacity model, further supporting a key role of Armcx1 in regulating neuronal injury responses in the adult central nervous system (CNS). Our findings suggest that Armcx1 controls mitochondrial transport during neuronal repair.
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