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Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1
Science ( IF 44.7 ) Pub Date : 2019-11-28 , DOI: 10.1126/science.aau2753
Ina Yoon 1 , Miso Nam 2 , Hoi Kyoung Kim 1 , Hee-Sun Moon 1 , Sungmin Kim 1 , Jayun Jang 3 , Ji Ae Song 3 , Seung Jae Jeong 1 , Sang Bum Kim 1 , Seongmin Cho 3 , YounHa Kim 3 , Jihye Lee 1 , Won Suk Yang 1 , Hee Chan Yoo 4 , Kibum Kim 4, 5 , Min-Sun Kim 2 , Aerin Yang 6 , Kyukwang Cho 6 , Hee-Sung Park 6 , Geum-Sook Hwang 2 , Kwang Yeon Hwang 7 , Jung Min Han 4, 5 , Jong Hyun Kim 1 , Sunghoon Kim 1, 3
Affiliation  

A tRNA synthase in metabolic control Leucyl-tRNA synthetase 1 (LARS1), which covalently couples leucine to its cognate transfer RNAs (tRNAs), appears to have broader roles in the control of leucine metabolism. The enzyme also serves as a leucine sensor for the mechanistic target of rapamycin complex 1 (mTORC1), which regulates protein synthesis, metabolism, autophagy, and cell growth. Yoon et al. show that in cells deprived of glucose, LARS1 is phosphorylated by Unc-51 like autophagy activating kinase 1 (see the Perspective by Lehman and Abraham). This phosphorylation decreases leucine binding to LARS1 and, in turn, should decrease translation, reduce activation of mTORC1, and perhaps free up leucine for use in the generation of adenosine triphosphate in glucose-starved cells. Science, this issue p. 205; see also p. 146 Leucine binding to leucyl-tRNA synthetase (LARS1) is controlled by phosphorylation of LARS1. Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 (LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine binding. The phosphorylated LARS1 showed decreased leucine binding, which may inhibit protein synthesis and help save energy. Leucine that is not used for anabolic processes may be available for catabolic pathway energy generation. The LARS1-mediated changes in leucine utilization might help support cell survival under glucose deprivation. Thus, depending on glucose availability, LARS1 may help regulate whether leucine is used for protein synthesis or energy production.

中文翻译:

亮氨酸-tRNA合成酶1对亮氨酸代谢的葡萄糖依赖性控制

代谢控制中的 tRNA 合酶亮氨酸-tRNA 合成酶 1 (LARS1) 将亮氨酸与其同源转移 RNA (tRNA) 共价偶联,似乎在控制亮氨酸代谢中具有更广泛的作用。该酶还可作为雷帕霉素复合物 1 (mTORC1) 的机械靶标的亮氨酸传感器,其调节蛋白质合成、代谢、自噬和细胞生长。尹等人。表明在缺乏葡萄糖的细胞中,LARS1 像自噬激活激酶 1 一样被 Unc-51 磷酸化(参见 Lehman 和 Abraham 的观点)。这种磷酸化减少了亮氨酸与 LARS1 的结合,反过来,应该减少翻译,减少 mTORC1 的激活,并可能释放亮氨酸用于在葡萄糖饥饿细胞中生成三磷酸腺苷。科学,这个问题 p。205; 另见第。146 亮氨酸与亮氨酰 tRNA 合成酶 (LARS1) 的结合受 LARS1 的磷酸化控制。尽管葡萄糖和氨基酸对能量代谢很重要,但两种营养素之间的相互作用尚不清楚。我们为亮氨酸-tRNA 合成酶 1 (LARS1) 在亮氨酸使用的葡萄糖依赖性控制中的作用提供了证据。在葡萄糖饥饿时,LARS1 在对亮氨酸结合至关重要的残基处被 Unc-51 磷酸化,如自噬激活激酶 1 (ULK1)。磷酸化的 LARS1 显示亮氨酸结合减少,这可能会抑制蛋白质合成并有助于节省能量。不用于合成代谢过程的亮氨酸可用于分解代谢途径能量产生。LARS1 介导的亮氨酸利用变化可能有助于支持葡萄糖剥夺下的细胞存活。因此,
更新日期:2019-11-28
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