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Myung, Kyungjae
Center for Genomic Integrity
Research Interests
  • DNA Replication, DNA Repair, DNA Recombination, DNA Damage Response, cancer, aging

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O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine

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Title
O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine
Author
Kim, KibumYoo, Hee ChanKim, Byung GyuKim, SulheeSung, YulseungYoon, InaYu, Ya ChunPark, Seung JoonKim, Jong HyunMyung, KyungjaeHwang, Kwang YeonKim, SunghoonHan, Jung Min
Issue Date
2022-05
Publisher
NATURE PORTFOLIO
Citation
NATURE COMMUNICATIONS, v.13, no.1, pp.2904
Abstract
All living organisms have the ability to sense nutrient levels to coordinate cellular metabolism. Despite the importance of nutrient-sensing pathways that detect the levels of amino acids and glucose, how the availability of these two types of nutrients is integrated is unclear. Here, we show that glucose availability regulates the central nutrient effector mTORC1 through intracellular leucine sensor leucyl-tRNA synthetase 1 (LARS1). Glucose starvation results in O-GlcNAcylation of LARS1 on residue S1042. This modification inhibits the interaction of LARS1 with RagD GTPase and reduces the affinity of LARS1 for leucine by promoting phosphorylation of its leucine-binding site by the autophagy-activating kinase ULK1, decreasing mTORC1 activity. The lack of LARS1 O-GlcNAcylation constitutively activates mTORC1, supporting its ability to sense leucine, and deregulates protein synthesis and leucine catabolism under glucose starvation. This work demonstrates that LARS1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine. Leucyl-tRNA synthetase 1 (LARS1) is a leucine sensor for mTORC1 signaling and regulates leucine utilization depending on glucose availability. Here, the author show that O-GlcNAcylation of LARS1 is crucial for its ability to regulate mTORC1 activity and leucine metabolism upon glucose starvation.
URI
https://scholarworks.unist.ac.kr/handle/201301/59330
URL
https://www.nature.com/articles/s41467-022-30696-8
DOI
10.1038/s41467-022-30696-8
ISSN
2041-1723
Appears in Collections:
BME_Journal Papers
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