Journal
CELL DEATH AND DIFFERENTIATION
Volume 21, Issue 8, Pages 1198-1208Publisher
SPRINGERNATURE
DOI: 10.1038/cdd.2014.35
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Funding
- Fondazione Italiana Sclerosi Multipla (FISM) [2010/B/1, 2012/B/11, FISM 2008/R/18]
- Italian Ministry of Health
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- Polish National Science Centre [UMO-2011/01/M/NZ3/02128]
- BIO-IMAGing in Research Innovation and Education [FP7-REGPOT-2010-1]
- Foundation for Polish Science (FNP)
- UE
- European Regional Development Fund
- Operational Programme 'Innovative Economy'
- Italian Ministry of Education
- CNR project 'Aging'
- AIRC
- Telethon [GGP11139B]
- Italian Ministry of Education, University and Research
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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-alpha) 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-a exposure and inhibit OPC differentiation. Overall, our data indicate that TNF-alpha induces metabolic changes, driven by mitochondrial impairment and AMPK activation, leading to the inhibition of OPC differentiation.
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