한빛사논문
- 조회822
Kibum Kim1,2,10, Hee Chan Yoo2,10, Byung Gyu Kim3, Sulhee Kim4, Yulseung Sung2, Ina Yoon2,5,6, Ya Chun Yu2, Seung Joon Park1,2, Jong Hyun Kim7, Kyungjae Myung3,8, Kwang Yeon Hwang4, Sunghoon Kim2,5,6 & Jung Min Han1,2,9,*
1Interdisciplinary Program of Integrated OMICS for Biomedical Science, Graduate School, Yonsei University, Seoul 03722, South Korea. 2Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon 21983, South Korea. 3Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, South Korea. 4Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea. 5Institute for Artificial Intelligence and Biomedical Research, Medicinal Bioconvergence Research Center, Yonsei University, Incheon 21983, South Korea. 6College of Medicine, Gangnam Severance Hospital, Yonsei University, Seoul 06273, South Korea. 7Department of Biochemistry, School of Medicine, Catholic University of Daegu, Daegu 42472, South Korea. 8Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, South Korea. 9POSTECH Biotech Center, Pohang University of Science and Technology, Pohang 37673, South Korea. 10These authors contributed equally: Kibum Kim, Hee Chan Yoo.
*Corresponding author.
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.
논문정보
- Research article
- 2022년 05월 (BRIC 등록일 2022-05-31)
- 국내(교신)+국외 연구진
- 생명과학 > 노화/암생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
관련분야 논문보기
해당논문 저자보기
