Metabolic Enhancement of Glycolysis and Mitochondrial Respiration Are Essential for Neuronal Differentiation

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.