Metabolic reactions provide energy and metabolic substance for cell function. It was recently shown that metabolic reprogramming is a key regulator of cell pluripotency and differentiation. Although many evidences point to a metabolic “switch” toward mitochondrial respiration, the importance of glycolysis and mitochondrial respiration is still controversial. In this study, we differentiated two different neuronal cells and compared the glycolytic and metabolic profile before and after differentiation. The results showed a significant increase in glycolysis (includes basal glycolysis and glycolytic capacity) and mitochondrial respiration (includes mitochondrial basal respiration, adenosine triphosphate production, and mitochondrial respiration capacity) of both SY5Y and neural stem cells (NSCs) during neuronal differentiation, whereas their mitochondrial DNA copies remain unchanged. Antimycin, a mitochondrial inhibitor, reduced cell density of differentiated SY5Y cells. However, for differentiated NSCs, antimycin dedifferentiated the cells, resulted in a significant increase in cell density, and lowered oxidative stress. In conclusion, this study demonstrated that metabolic enhancement of glycolysis and mitochondrial respiration (rather than a “switch”) are both important for neuronal differentiation, although only the blocking of mitochondrial respiration reverses the differentiation process.

中文翻译：

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糖酵解和线粒体呼吸的代谢增强对于神经元分化至关重要

代谢反应为细胞功能提供能量和代谢物质。最近表明，代谢重编程是细胞多能性和分化的关键调节因子。尽管许多证据表明代谢“转换”为线粒体呼吸，但糖酵解和线粒体呼吸的重要性仍然存在争议。在这项研究中，我们分化了两种不同的神经元细胞，并比较了分化前后的糖酵解和代谢特征。结果显示，在神经元分化过程中，SY5Y 和神经干细胞 (NSC) 的糖酵解（包括基础糖酵解和糖酵解能力）和线粒体呼吸（包括线粒体基础呼吸、三磷酸腺苷产生和线粒体呼吸能力）显着增加，而它们的线粒体DNA拷贝保持不变。Antimycin 是一种线粒体抑制剂，可降低分化的 SY5Y 细胞的细胞密度。然而，对于分化的 NSC，抗霉素使细胞去分化，导致细胞密度显着增加，并降低了氧化应激。总之，这项研究表明，糖酵解和线粒体呼吸的代谢增强（而不是“开关”）对于神经元分化都很重要，尽管只有线粒体呼吸的阻断才能逆转分化过程。