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

Ina Yoon, Miso Nam, Hoi Kyoung Kim, Hee-Sun Moon, Sungmin Kim, Jayun Jang, Ji Ae Song, Seung Jae Jeong, Sang Bum Kim, Seongmin Cho, YounHa Kim, Jihye Lee, Won Suk Yang, Hee Chan Yoo, Kibum Kim, Min-Sun Kim, Aerin Yang, Kyukwang Cho, Hee-Sung Park, Geum-Sook Hwang, Kwang Yeon Hwang, Jung Min Han, Jong Hyun Kim, and Sunghoon Kim

Abstract

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.

Article Site: https://science.sciencemag.org/content/367/6474/205

Original Document: https://science.sciencemag.org/content/367/6474/205.full.pdf

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