Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1

• Published in: Science (American Association for the Advancement of Science) Vol. 367; no. 6474; pp. 205 - 210
• Main Authors: Yoon, Ina, Nam, Miso, Kim, Hoi Kyoung, Moon, Hee-Sun, Kim, Sungmin, Jang, Jayun, Song, Ji Ae, Jeong, Seung Jae, Kim, Sang Bum, Cho, Seongmin, Kim, YounHa, Lee, Jihye, Yang, Won Suk, Yoo, Hee Chan, Kim, Kibum, Kim, Min-Sun, Yang, Aerin, Cho, Kyukwang, Park, Hee-Sung, Hwang, Geum-Sook, Hwang, Kwang Yeon, Han, Jung Min, Kim, Jong Hyun, Kim, Sunghoon
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 10.01.2020
• Subjects: Animals; Autophagy; Autophagy-Related Protein-1 Homolog - genetics; Autophagy-Related Protein-1 Homolog - metabolism; Energy; Energy Metabolism; Fibroblasts; Glucose - metabolism; HEK293 Cells; HeLa Cells; Humans; Leucine; Leucine - metabolism; Leucine-tRNA ligase; Leucine-tRNA Ligase - metabolism; Lysosomes - metabolism; Mechanistic Target of Rapamycin Complex 1 - metabolism; Metabolism; Mice; Monomeric GTP-Binding Proteins - metabolism; Phosphorylation; Protein synthesis; Proteins; Signal Transduction; tRNA Leu
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aau2753

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.