Mitochondrial dysfunction increases fatty acid β‐oxidation and translates into impaired neuroblast maturation.

The metabolic transition from anaerobic glycolysis and fatty acid β‐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 β‐oxidation as a peculiar feature of neuroblasts with altered mitochondria. The consequent metabolic switch favors neuroblast proliferation at the expense of neuron maturation. [ABSTRACT FROM AUTHOR]