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.
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DOI：
10.4049/jimmunol.1302498
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发表时间：
2014-09-15
期刊：
影响因子：
--
通讯作者：
Pearce EJ
中科院分区：
文献类型：
--
作者：
Amiel E;Everts B;Fritz D;Beauchamp S;Ge B;Pearce EL;Pearce EJ
TLR介导的树突状细胞(DCs)激活与代谢转变有关，在代谢转变中，内源性NO抑制线粒体氧化磷酸化，细胞为了生存而致力于葡萄糖和有氧糖酵解。我们发现，抑制雷帕霉素的机械靶点(MTOR)通过抑制TLR激活的DC的NO产生的诱导，从而延长了DC的寿命，从而允许细胞继续使用他们的线粒体来产生ATP，并允许他们灵活地使用脂肪酸或葡萄糖作为营养物质来促进核心代谢。这些数据为mTOR如何在TLR激活后调节DC新陈代谢和细胞寿命提供了新的机制见解，并为先前发现的mTOR抑制增强DC在自体疫苗接种中的效力提供了解释。
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.
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影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
DOI：
10.1042/bj20111451
发表时间：
2012-01-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Lee J;Giordano S;Zhang J
通讯作者：
Zhang J
影响因子：
20.3
作者：
Hackstein, H;Taner, T;Thomson, AW
通讯作者：
Thomson, AW
DOI：
10.1073/pnas.90.7.3038
发表时间：
1993-04-01
影响因子：
11.1
作者：
INABA, K;INABA, M;STEINMAN, RM
通讯作者：
STEINMAN, RM
影响因子：
20.3
作者：
Everts, Bart;Amiel, Eyal;Pearce, Edward J.
通讯作者：
Pearce, Edward J.