Mitochondrial dysfunction increases fatty acid β-oxidation and translates into impaired neuroblast maturation
Mitochondrial dysfunction increases fatty acid β-oxidation and translates into impaired neuroblast maturation
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DOI：
10.1002/1873-3468.13584
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发表时间：
2019-08-31
期刊：
影响因子：
3.5
通讯作者：
Mitro, Nico
中科院分区：
文献类型：
--
作者：
Audano, Matteo;Pedretti, Silvia;Mitro, Nico
从无氧糖酵解和脂肪酸β-氧化到糖酵解耦合氧化磷酸化的代谢转变是静止神经干细胞向增殖性神经祖细胞转变的关键过程。然而，在神经发生的最后一步（从神经母细胞到神经元成熟）中代谢转变和线粒体参与的完整表征仍然难以捉摸。在这里，我们描述了神经母细胞 Neuro2a 细胞的模型，由于线粒体功能障碍，其分化能力受损。使用由稳态代谢组学和代谢流分析组成的详细生化特征，我们发现脂肪酸β-氧化增加是线粒体改变的神经母细胞的一个独特特征。随后的代谢转变有利于神经母细胞增殖，但代价是神经元成熟。
The metabolic transition from anaerobic glycolysis and fatty acid beta-oxidation to glycolysis coupled to oxidative phosphorylation is a key process for the transition of quiescent neural stem cells to proliferative neural progenitor cells. However, a full characterization of the metabolic shift and the involvement of mitochondria during the last step of neurogenesis, from neuroblasts to neuron maturation, is still elusive. Here, we describe a model of neuroblasts, Neuro2a cells, with impaired differentiation capacity due to mitochondrial dysfunction. Using a detailed biochemical characterization consisting of steady-state metabolomics and metabolic flux analysis, we find increased fatty acid beta-oxidation as a peculiar feature of neuroblasts with altered mitochondria. The consequent metabolic switch favors neuroblast proliferation at the expense of neuron maturation.