Tumor necrosis factor-α impairs oligodendroglial differentiation through a mitochondria-dependent process

M. Bonora, E. De Marchi, S. Patergnani, J. M. Suski, F. Celsi, A. Bononi, C. Giorgi, S. Marchi, A. Rimessi, J. Duszyński, T. Pozzan, M. R. Wieckowski, P. Pinton

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondrial defects, affecting parameters such as mitochondrial number and shape, levels of respiratory chain complex components and markers of oxidative stress, have been associated with the appearance and progression of multiple sclerosis. Nevertheless, mitochondrial physiology has never been monitored during oligodendrocyte progenitor cell (OPC) differentiation, especially in OPCs challenged with proinflammatory cytokines. Here, we show that tumor necrosis factor alpha (TNF-α) inhibits OPC differentiation, accompanied by altered mitochondrial calcium uptake, mitochondrial membrane potential, and respiratory complex I activity as well as increased reactive oxygen species production. Treatment with a mitochondrial uncoupler (FCCP) to mimic mitochondrial impairment also causes cells to accumulate at the progenitor stage. Interestingly, AMP-activated protein kinase (AMPK) levels increase during TNF-α exposure and inhibit OPC differentiation. Overall, our data indicate that TNF-α induces metabolic changes, driven by mitochondrial impairment and AMPK activation, leading to the inhibition of OPC differentiation.

Original languageEnglish
Pages (from-to)1198-1208
Number of pages11
JournalCell Death and Differentiation
Volume21
Issue number8
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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