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; Youn Ha 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; Sunghoon Kim

doi:10.1126/science.aau2753

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, Youn Ha Kim, Jihye Lee, Won Suk Yang, Hee Chan Yoo, Kibum Kim, Min Sun Kim, Aerin Yang, Kyukwang Cho, Hee Sung Park, Geum Sook HwangKwang Yeon Hwang, Jung Min Han, Jong Hyun Kim, Sunghoon Kim

Research output: Contribution to journal › Article › peer-review

65 Citations (Scopus)

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.

Original language	English
Pages (from-to)	205-210
Number of pages	6
Journal	Science
Volume	367
Issue number	6474
DOIs	https://doi.org/10.1126/science.aau2753
Publication status	Published - 2020 Jan 10

Bibliographical note

Funding Information:
We thank H.-S. Jeong for supplying AMPKg1 null 293A cells. Funding: This work was supported by the Global Frontier Project grant [NRF-M3A6A4-2010-0029785 (Sunghoon Kim), NRF-2014M3A6A4075060 (H.-S.P.), NRF-2015M3A6A4076702 (G.-S.H.), and NRF-2013M3A6A4044795 (K.Y.H.)] of the National Research Foundation funded by the Ministry of Science and ICT (MSIT) of Korea; the Korea Basic Science Institute (T39720) (G.-S.H.); and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education [2018R1A6A1A03023718 (J.M.H.)].

Publisher Copyright:
© 2020 American Association for the Advancement of Science. All rights reserved.

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Yoon, I., Nam, M., Kim, H. K., Moon, H. S., Kim, S., Jang, J., Song, J. A., Jeong, S. J., Kim, S. B., Cho, S., Kim, Y. H., Lee, J., Yang, W. S., Yoo, H. C., Kim, K., Kim, M. S., Yang, A., Cho, K., Park, H. S., ... Kim, S. (2020). Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1. Science, 367(6474), 205-210. https://doi.org/10.1126/science.aau2753

Yoon, I, Nam, M, Kim, HK, Moon, HS, Kim, S, Jang, J, Song, JA, Jeong, SJ, Kim, SB, Cho, S, Kim, YH, Lee, J, Yang, WS, Yoo, HC, Kim, K, Kim, MS, Yang, A, Cho, K, Park, HS, Hwang, GS, Hwang, KY, Han, JM, Kim, JH & Kim, S 2020, 'Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1', Science, vol. 367, no. 6474, pp. 205-210. https://doi.org/10.1126/science.aau2753

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title = "Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1",

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.",

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

note = "Funding Information: We thank H.-S. Jeong for supplying AMPKg1 null 293A cells. Funding: This work was supported by the Global Frontier Project grant [NRF-M3A6A4-2010-0029785 (Sunghoon Kim), NRF-2014M3A6A4075060 (H.-S.P.), NRF-2015M3A6A4076702 (G.-S.H.), and NRF-2013M3A6A4044795 (K.Y.H.)] of the National Research Foundation funded by the Ministry of Science and ICT (MSIT) of Korea; the Korea Basic Science Institute (T39720) (G.-S.H.); and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education [2018R1A6A1A03023718 (J.M.H.)]. Publisher Copyright: {\textcopyright} 2020 American Association for the Advancement of Science. All rights reserved.",

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AU - Yoon, Ina

AU - Nam, Miso

AU - Kim, Hoi Kyoung

AU - Moon, Hee Sun

AU - Kim, Sungmin

AU - Jang, Jayun

AU - Song, Ji Ae

AU - Jeong, Seung Jae

AU - Kim, Sang Bum

AU - Cho, Seongmin

AU - Kim, Youn Ha

AU - Lee, Jihye

AU - Yang, Won Suk

AU - Yoo, Hee Chan

AU - Kim, Kibum

AU - Kim, Min Sun

AU - Yang, Aerin

AU - Cho, Kyukwang

AU - Park, Hee Sung

AU - Hwang, Geum Sook

AU - Hwang, Kwang Yeon

AU - Han, Jung Min

AU - Kim, Jong Hyun

AU - Kim, Sunghoon

N1 - Funding Information: We thank H.-S. Jeong for supplying AMPKg1 null 293A cells. Funding: This work was supported by the Global Frontier Project grant [NRF-M3A6A4-2010-0029785 (Sunghoon Kim), NRF-2014M3A6A4075060 (H.-S.P.), NRF-2015M3A6A4076702 (G.-S.H.), and NRF-2013M3A6A4044795 (K.Y.H.)] of the National Research Foundation funded by the Ministry of Science and ICT (MSIT) of Korea; the Korea Basic Science Institute (T39720) (G.-S.H.); and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education [2018R1A6A1A03023718 (J.M.H.)]. Publisher Copyright: © 2020 American Association for the Advancement of Science. All rights reserved.

PY - 2020/1/10

Y1 - 2020/1/10

N2 - 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.

AB - 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.

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ER -

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

Abstract

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