Metabolic reprogramming during neuronal differentiation.
Metabolic reprogramming during neuronal differentiation.
复制标题
神经元分化过程中的代谢重编程
DOI：
10.1038/cdd.2016.36
复制
发表时间：
2016-09-01
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
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作者：
新产生的神经元经过一系列明确的发育阶段，使它们能够整合到现有的神经元回路中。有丝分裂后的神经元在退出细胞周期后，经历神经元迁移、轴突伸长、轴突修剪、树突形态发生以及突触成熟和可塑性。在早期皮质神经元发育过程中缺乏全局代谢分析，导致我们探索原代皮质神经元离体分化过程中细胞代谢和线粒体生物学的作用。出乎意料的是，我们观察到线粒体生物合成的巨大增加。线粒体质量、形态和功能的变化与线粒体生物发生的主要调节因子TFAM和PGC-1α的上调相关。伴随着线粒体生物合成，我们观察到在神经元分化过程中葡萄糖代谢的增加，这与葡萄糖摄取的增加和增强的GLUT 3 mRNA表达和磷酸果糖激酶1（PFKp）蛋白表达的血小板亚型有关。此外，谷氨酸-谷氨酰胺代谢也增加皮层神经元的分化过程中。我们鉴定PI 3 K-Akt-mTOR信号传导作为神经元中能量代谢的关键调节器作用。这些代谢途径的选择性药理学抑制表明存在需要满足以允许神经元分化的代谢检查点。
Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate–glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K–Akt–mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.
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影响因子：
9
作者：
通讯作者：
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影响因子：
12.4
作者：
Bonora, M.;De Marchi, E.;Pinton, P.
通讯作者：
Pinton, P.
影响因子：
9
作者：
Gioran A;Nicotera P;Bano D
通讯作者：
Bano D
影响因子：
12.4
作者：
通讯作者：
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影响因子：
9
作者：
通讯作者：
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