Han Sung Min, Baig Huma S, Hammarlund Marc
Departments of Genetics and Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Departments of Genetics and Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Neuron. 2016 Dec 21;92(6):1308-1323. doi: 10.1016/j.neuron.2016.11.025.
Axon regeneration is essential to restore the nervous system after axon injury. However, the neuronal cell biology that underlies axon regeneration is incompletely understood. Here we use in vivo, single-neuron analysis to investigate the relationship between nerve injury, mitochondrial localization, and axon regeneration. Mitochondria translocate into injured axons so that average mitochondria density increases after injury. Moreover, single-neuron analysis reveals that axons that fail to increase mitochondria have poor regeneration. Experimental alterations to axonal mitochondrial distribution or mitochondrial respiratory chain function result in corresponding changes to regeneration outcomes. Axonal mitochondria are specifically required for growth-cone migration, identifying a key energy challenge for injured neurons. Finally, mitochondrial localization to the axon after injury is regulated in part by dual-leucine zipper kinase 1 (DLK-1), a conserved regulator of axon regeneration. These data identify regulation of axonal mitochondria as a new cell-biological mechanism that helps determine the regenerative response of injured neurons.
轴突再生对于轴突损伤后恢复神经系统至关重要。然而，轴突再生所依据的神经元细胞生物学仍未被完全理解。在此，我们运用体内单神经元分析来研究神经损伤、线粒体定位与轴突再生之间的关系。线粒体转移至受损轴突，使得损伤后线粒体平均密度增加。此外，单神经元分析显示，未能增加线粒体的轴突再生能力较差。对轴突线粒体分布或线粒体呼吸链功能进行实验性改变会导致再生结果相应变化。轴突线粒体是生长锥迁移所特别必需的，这确定了受损神经元面临的关键能量挑战。最后，损伤后线粒体向轴突的定位部分受双亮氨酸拉链激酶1（DLK-1）调控，DLK-1是轴突再生的保守调节因子。这些数据确定轴突线粒体的调控是一种新的细胞生物学机制，有助于确定受损神经元的再生反应。
