Resistance of glia-like central and peripheral neural stem cells to genetically induced mitochondrial dysfunction--differential effects on neurogenesis

Blanca Díaz-Castro, Ricardo Pardal, Paula García-Flores, Verónica Sobrino, Rocío Durán, José I Piruat, José López-Barneo

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondria play a central role in stem cell homeostasis. Reversible switching between aerobic and anaerobic metabolism is critical for stem cell quiescence, multipotency, and differentiation, as well as for cell reprogramming. However, the effect of mitochondrial dysfunction on neural stem cell (NSC) function is unstudied. We have generated an animal model with homozygous deletion of the succinate dehydrogenase subunit D gene restricted to cells of glial fibrillary acidic protein lineage (hGFAP-SDHD mouse). Genetic mitochondrial damage did not alter the generation, maintenance, or multipotency of glia-like central NSCs. However, differentiation to neurons and oligodendrocytes (but not to astrocytes) was impaired and, hence, hGFAP-SDHD mice showed extensive brain atrophy. Peripheral neuronal populations were normal in hGFAP-SDHD mice, thus highlighting their non-glial (non hGFAP(+)) lineage. An exception to this was the carotid body, an arterial chemoreceptor organ atrophied in hGFAP-SDHD mice. The carotid body contains glia-like adult stem cells, which, as for brain NSCs, are resistant to genetic mitochondrial damage.

Original languageEnglish
Pages (from-to)1511-9
Number of pages9
JournalEMBO Reports
Volume16
Issue number11
DOIs
Publication statusPublished - Nov 2015

Keywords

  • Animals
  • Astrocytes/physiology
  • Brain/abnormalities
  • Carotid Body/cytology
  • Disease Models, Animal
  • Gene Deletion
  • Glial Fibrillary Acidic Protein/metabolism
  • Mice
  • Mitochondria/genetics
  • Neural Stem Cells/cytology
  • Neurogenesis
  • Neuroglia/cytology
  • Neurons/physiology
  • Oligodendroglia/physiology
  • Succinate Dehydrogenase/genetics

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