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.

Mitochondrial dysfunction increases fatty acid β-oxidation and translates into impaired neuroblast maturation / M. Audano, S. Pedretti, M. Crestani, D. Caruso, E. De Fabiani, N. Mitro. - In: FEBS LETTERS. - ISSN 0014-5793. - 593:22(2019 Nov), pp. 3173-3189. [10.1002/1873-3468.13584]

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

M. Audano;S. Pedretti;M. Crestani;D. Caruso;E. De Fabiani
;
N. Mitro
2019

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.
energy metabolism; mitochondria; Neuro2a cells; neuron maturation
Settore BIO/10 - Biochimica
   Impact of blunted fatty acid synthesis on the develipment of diabetic peripheral neuropathy: deciphering the role of the lipogenic factor SREBP-1c
   FONDAZIONE CARIPLO
   2014-0991
nov-2019
Article (author)
File in questo prodotto:
File Dimensione Formato  
Audano M. et al authors preprint (before revision) .pdf

accesso aperto

Tipologia: Pre-print (manoscritto inviato all'editore)
Dimensione 1.81 MB
Formato Adobe PDF
1.81 MB Adobe PDF Visualizza/Apri
Audano_et_al-2019-FEBS_Letters.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.3 MB
Formato Adobe PDF
1.3 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/675204
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 12
social impact