Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation

被引:146
作者
Tan, Hayden Weng Siong [1 ]
Sim, Arthur Yi Loong [1 ]
Long, Yun Chau [1 ]
机构
[1] Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, Singapore, Singapore
关键词
AMMONIA-INDUCED AUTOPHAGY; RIBOSOMAL-PROTEIN S6; LEUCINE; NETWORK; RAT;
D O I
10.1038/s41467-017-00369-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Activation of autophagy and elevation of glutamine synthesis represent key adaptations to maintain amino acid balance during starvation. In this study, we investigate the role of autophagy and glutamine on the regulation of mTORC1, a critical kinase that regulates cell growth and proliferation. We report that supplementation of glutamine alone is sufficient to restore mTORC1 activity during prolonged amino acid starvation. Inhibition of autophagy abolishes the restorative effect of glutamine, suggesting that reactivation of mTORC1 is autophagy-dependent. Inhibition of glutaminolysis or transamination impairs glutamine-mediated mTORC1 reactivation, suggesting glutamine reactivates mTORC1 specifically through its conversion to glutamate and restoration of non-essential amino acid pool. Despite a persistent drop in essential amino acid pool during amino acid starvation, crosstalk between glutamine and autophagy is sufficient to restore insulin sensitivity of mTORC1. Thus, glutamine metabolism and autophagy constitute a specific metabolic program which restores mTORC1 activity during amino acid starvation.
引用
收藏
页数:10
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