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Leucine Signals to mTORC1 via Its Metabolite Acetyl-Coenzyme A

Authors
 Sung Min Son  ;  So Jung Park  ;  Huikyong Lee  ;  Farah Siddiqi  ;  Jong Eun Lee  ;  Fiona M. Menzies  ;  David C. Rubinsztein 
Citation
 CELL METABOLISM, Vol.29(1) : 192-201.e7, 2019 
Journal Title
 CELL METABOLISM 
ISSN
 1550-4131 
Issue Date
2019
Keywords
Raptor ; acetyl-CoA amino acid sensing ; autophagy ; leucine ; mTOR ; starvation
Abstract
The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of cell growth and metabolism. Leucine (Leu) activates mTORC1 and many have tried to identify the mechanisms whereby cells sense Leu in this context. Here we describe that the Leu metabolite acetyl-coenzyme A (AcCoA) positively regulates mTORC1 activity by EP300-mediated acetylation of the mTORC1 regulator, Raptor, at K1097. Leu metabolism and consequent mTORC1 activity are regulated by intermediary enzymes. As AcCoA is a Leu metabolite, this process directly correlates with Leu abundance, and does not require Leu sensing via intermediary proteins, as has been described previously. Importantly, we describe that this pathway regulates mTORC1 in a cell-type-specific manner. Finally, we observed decreased acetylated Raptor, and inhibited mTORC1 and EP300 activity in fasted mice tissues. These results provide a direct mechanism for mTORC1 regulation by Leu metabolism.
Files in This Item:
T201900195.pdf Download
DOI
10.1016/j.cmet.2018.08.013
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167623
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