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  • Mechanistic target of rapamycin inhibition extends cellular lifespan in dendritic cells by preserving mitochondrial function.

Mechanistic target of rapamycin inhibition extends cellular lifespan in dendritic cells by preserving mitochondrial function.

Journal of immunology (Baltimore, Md. : 1950) (2014-08-12)
Eyal Amiel, Bart Everts, Daniel Fritz, Saritha Beauchamp, Burong Ge, Erika L Pearce, Edward J Pearce
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Rotenone, ≥95%
Sigma-Aldrich
6-Diazo-5-oxo-L-norleucine, crystalline
Supelco
Rotenone, PESTANAL®, analytical standard
Sigma-Aldrich
KU 0063794, ≥98% (HPLC)