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

FEBS Lett. 2019 Nov;593(22):3173-3189. doi: 10.1002/1873-3468.13584. Epub 2019 Aug 31.

Abstract

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.

Keywords: Neuro2a cells; energy metabolism; mitochondria; neuron maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation
  • Energy Metabolism
  • Fatty Acids / metabolism*
  • Humans
  • Metabolomics
  • Mitochondria / metabolism*
  • Models, Biological
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Oxidation-Reduction

Substances

  • Fatty Acids