mTOR at the nexus of nutrition, growth, ageing and disease

被引:1705
作者
Liu, Grace Y. [1 ,2 ,3 ,4 ]
Sabatini, David M. [1 ,2 ,3 ,4 ]
机构
[1] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA
[2] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA
[3] Broad Inst, Cambridge, MA 02142 USA
[4] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA
基金
美国国家卫生研究院;
关键词
P70; S6; KINASE; TUMOR-SUPPRESSOR COMPLEX; AMINO-ACID SUFFICIENCY; RIBOSOMAL-PROTEIN S6; LIFE-SPAN EXTENSION; MAMMALIAN TARGET; RAG GTPASES; TUBEROUS SCLEROSIS; DEPENDENT ACTIVATION; PHOSPHOPROTEOME REVEALS;
D O I
10.1038/s41580-019-0199-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The mTOR pathway integrates a diverse set of environmental cues, such as growth factor signals and nutritional status, to direct eukaryotic cell growth. Over the past two and a half decades, mapping of the mTOR signalling landscape has revealed that mTOR controls biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Given the pathway's central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing. In this Review, we highlight recent advances in our understanding of the complex regulation of the mTOR pathway and discuss its function in the context of physiology, human disease and pharmacological intervention. The mTOR pathway integrates diverse environmental cues to control biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing, and is thus a promising target for pharmacological intervention.
引用
收藏
页码:183 / 203
页数:21
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