Mechanistic target of rapamycin inhition extend cellular lifespan in dendritic 
cells by preserving mitochondrial function

Amiel, Eyal; Everts, Bart; Fritz, Daniel; Beauchamp, Saritha; Ge, Burong; Pearce, Erika L.; Pearce, Edward J.

doi:org/10.4049/jimmunol.1302498

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Mechanistic target of rapamycin inhition extend cellular lifespan in dendritic cells by preserving mitochondrial function

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Pearce, Erika L.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce, Edward J.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.jimmunol.org/content/193/6/2821.long
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Citation

Amiel, E., Everts, B., Fritz, D., Beauchamp, S., Ge, B., Pearce, E. L., et al. (2014). Mechanistic target of rapamycin inhition extend cellular lifespan in dendritic cells by preserving mitochondrial function. The Journal of Immunology, 193, 2821-2830. doi:org/10.4049/jimmunol.1302498.

Cite as: https://hdl.handle.net/21.11116/0000-0006-614F-5

Abstract

TLR-mediated activation of dendritic cells (DCs) is associated with a metabolic transition in which mitochondrial oxidative phosphorylation is inhibited by endogenously synthesized NO and the cells become committed to glucose and aerobic glycolysis for survival. We show that inhibition of mechanistic target of rapamycin (mTOR) extends the lifespan of TLR-activated DCs by inhibiting the induction of NO production, thereby allowing the cells to continue to use their mitochondria to generate ATP, and allowing them the flexibility to use fatty acids or glucose as nutrients to fuel core metabolism. These data provide novel mechanistic insights into how mTOR modulates DC metabolism and cellular longevity following TLR activation and provide an explanation for previous findings that mTOR inhibition enhances the efficacy of DCs in autologous vaccination.