Differential Mitochondrial Requirements for Radially and Non-radially Migrating Cortical Neurons: Implications for Mitochondrial Disorders

Cell Rep. 2016 Apr 12;15(2):229-37. doi: 10.1016/j.celrep.2016.03.024. Epub 2016 Mar 31.

Abstract

Mitochondrial dysfunction has been increasingly linked to neurodevelopmental disorders such as intellectual disability, childhood epilepsy, and autism spectrum disorder, conditions also associated with cortical GABAergic interneuron dysfunction. Although interneurons have some of the highest metabolic demands in the postnatal brain, the importance of mitochondria during interneuron development is unknown. We find that interneuron migration from the basal forebrain to the neocortex is highly sensitive to perturbations in oxidative phosphorylation. Both pharmacologic and genetic inhibition of adenine nucleotide transferase 1 (Ant1) disrupts the non-radial migration of interneurons, but not the radial migration of cortical projection neurons. The selective dependence of cortical interneuron migration on oxidative phosphorylation may be a mechanistic pathway upon which multiple developmental and metabolic pathologies converge.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotide Translocator 1 / deficiency
  • Adenine Nucleotide Translocator 1 / metabolism
  • Animals
  • Cell Movement*
  • Centrosome / metabolism
  • Cerebral Cortex / pathology*
  • Embryo, Mammalian / pathology
  • Female
  • Interneurons / pathology
  • Male
  • Mice, Inbred C57BL
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / pathology*
  • Mutation / genetics
  • Neurons / metabolism*
  • Oxidative Phosphorylation

Substances

  • Adenine Nucleotide Translocator 1