Mitochondrial biogenesis is required for axonal growth
Mitochondrial biogenesis is required for axonal growth
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DOI：
10.1242/dev.128926
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发表时间：
2016-06-01
期刊：
影响因子：
4.6
通讯作者：
Kaasik, Allen
中科院分区：
文献类型：
--
作者：
Vaarmann, Annika;Mandel, Merle;Kaasik, Allen
在早期发育过程中，神经元经历复杂的形态重排，组装成神经元回路并传播信号。快速增长需要大量的建筑材料，高效的细胞内运输，以及相当大的能量。为了产生这种能量，神经元应该首先产生新的线粒体，因为先前存在的线粒体不太可能提供足够的ATP产生加速。在这里，我们证明了线粒体的生物发生和ATP的产生是培养的大鼠皮质神经元轴突生长和神经元发育所必需的。我们还证明了激活CaMKKβ、LKB1-Strad或TAK1通路的生长信号也共同激活了AMPK-PGC-1α-NRF1轴，从而产生新的线粒体，为即将到来的生长提供能量。总而言之，我们的结果表明，神经元能够为即将到来的能量需求发出信号。通过这些途径更早地激活线粒体生物发生将加速新线粒体的产生，从而确保在合成其他促进轴突生长的因素时的能量产生能力。
During early development, neurons undergo complex morphological rearrangements to assemble into neuronal circuits and propagate signals. Rapid growth requires a large quantity of building materials, efficient intracellular transport and also a considerable amount of energy. To produce this energy, the neuron should first generate new mitochondria because the pre-existing mitochondria are unlikely to provide a sufficient acceleration in ATP production. Here, we demonstrate that mitochondrial biogenesis and ATP production are required for axonal growth and neuronal development in cultured rat cortical neurons. We also demonstrate that growth signals activating the CaMKK beta, LKB1-STRAD or TAK1 pathways also co-activate the AMPK-PGC-1 alpha-NRF1 axis leading to the generation of new mitochondria to ensure energy for upcoming growth. In conclusion, our results suggest that neurons are capable of signalling for upcoming energy requirements. Earlier activation of mitochondrial biogenesis through these pathways will accelerate the generation of new mitochondria, thereby ensuring energy-producing capability for when other factors for axonal growth are synthesized.