TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast.
TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast.
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DOI：
10.1111/acel.12080
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发表时间：
2013-08
期刊：
影响因子：
7.8
通讯作者：
Bähler J
中科院分区：
文献类型：
--
作者：
Rallis C;Codlin S;Bähler J
雷帕霉素复合物 1 (TORC1) 的靶点与从酵母到人类的生长控制和衰老有关。裂殖酵母正在成为研究 TOR 信号传导的流行模型生物，尽管雷帕霉素被认为不会影响该生物的细胞生长。在这里，我们分析了雷帕霉素和咖啡因单独和组合对裂殖酵母中多个细胞过程的影响。这两种药物导致了依赖于 TORC1 抑制的多样化和特定表型，包括延长寿命、抑制全局翻译、抑制细胞生长和分裂以及模拟氮饥饿的全局基因表达重新编程。雷帕霉素和咖啡因对这些不同的 TORC1 依赖性过程有不同的影响。联合药物治疗增强了大多数表型并有效阻止了细胞生长。雷帕霉素对整体翻译的影响比咖啡因更微妙，而这两种药物都能有效延长时间寿命。雷帕霉素和咖啡因不会通过生长培养基的 pH 值影响寿命。雷帕霉素仅在生长期施用时才能延长非生长细胞的寿命，而在细胞停止增殖后施用则不会。雷帕霉素和咖啡因的剂量与生长抑制和寿命延长密切相关。这项综合分析将为未来对裂殖酵母及其他细胞中 TORC1 功能和细胞衰老的研究提供信息。
Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here, we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two drugs led to diverse and specific phenotypes that depended on TORC1 inhibition, including prolonged chronological lifespan, inhibition of global translation, inhibition of cell growth and division, and reprograming of global gene expression mimicking nitrogen starvation. Rapamycin and caffeine differentially affected these various TORC1-dependent processes. Combined drug treatment augmented most phenotypes and effectively blocked cell growth. Rapamycin showed a much more subtle effect on global translation than did caffeine, while both drugs were effective in prolonging chronological lifespan. Rapamycin and caffeine did not affect the lifespan via the pH of the growth media. Rapamycin prolonged the lifespan of nongrowing cells only when applied during the growth phase but not when applied after cells had stopped proliferation. The doses of rapamycin and caffeine strongly correlated with growth inhibition and with lifespan extension. This comprehensive analysis will inform future studies into TORC1 function and cellular aging in fission yeast and beyond.
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影响因子：
3.7
作者：
Calvo IA;Gabrielli N;Iglesias-Baena I;García-Santamarina S;Hoe KL;Kim DU;Sansó M;Zuin A;Pérez P;Ayté J;Hidalgo E
通讯作者：
Hidalgo E
影响因子：
21.3
作者：
Petersen, Janni;Nurse, Paul
通讯作者：
Nurse, Paul
影响因子：
4
作者：
Nakashima, Akio;Sato, Tatsuhiro;Tamanoi, Fuyuhiko
通讯作者：
Tamanoi, Fuyuhiko
影响因子：
3.3
作者：
Chen, DR;Toone, WM;Bähler, J
通讯作者：
Bähler, J
影响因子：
4
作者：
Alvarez, Beatriz;Moreno, Sergio
通讯作者：
Moreno, Sergio