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- W4385737526 abstract "Abstract Cell growth is regulated by the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which functions both as a nutrient sensor and a master controller of virtually all biosynthetic pathways. This ensures that cells are metabolically active only when conditions are optimal for growth. Notably, although mTORC1 is known to regulate fatty acid biosynthesis, how and whether the cellular lipid biosynthetic capacity signals back to fine-tune mTORC1 activity remains poorly understood. Here we show that mTORC1 senses the capacity of a cell to synthesise fatty acids by detecting the levels of malonyl-CoA, an intermediate of this biosynthetic pathway. We find that, in both yeast and mammalian cells, this regulation is direct, with malonyl-CoA binding to the mTOR catalytic pocket and acting as a specific ATP-competitive inhibitor. When fatty acid synthase (FASN) is downregulated/inhibited, elevated malonyl-CoA levels are channelled to proximal mTOR molecules that form direct protein–protein interactions with acetyl-CoA carboxylase 1 (ACC1) and FASN. Our findings represent a conserved and unique homeostatic mechanism whereby impaired fatty acid biogenesis leads to reduced mTORC1 activity to coordinately link this metabolic pathway to the overall cellular biosynthetic output. Moreover, they reveal the existence of a physiological metabolite that directly inhibits the activity of a signalling kinase in mammalian cells by competing with ATP for binding." @default.
- W4385737526 created "2023-08-11" @default.
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- W4385737526 date "2023-08-10" @default.
- W4385737526 modified "2023-10-05" @default.
- W4385737526 title "Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor" @default.
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- W4385737526 cites W1717375378 @default.
- W4385737526 cites W1919928987 @default.
- W4385737526 cites W1968403457 @default.
- W4385737526 cites W1968603215 @default.
- W4385737526 cites W1970741593 @default.
- W4385737526 cites W1976896999 @default.
- W4385737526 cites W1977709885 @default.
- W4385737526 cites W1981861340 @default.
- W4385737526 cites W1985799174 @default.
- W4385737526 cites W1986234170 @default.
- W4385737526 cites W1988764467 @default.
- W4385737526 cites W1990152592 @default.
- W4385737526 cites W1992962914 @default.
- W4385737526 cites W1997241169 @default.
- W4385737526 cites W2000281583 @default.
- W4385737526 cites W2001568034 @default.
- W4385737526 cites W2004582874 @default.
- W4385737526 cites W2006559495 @default.
- W4385737526 cites W2008517160 @default.
- W4385737526 cites W2010378383 @default.
- W4385737526 cites W2017541566 @default.
- W4385737526 cites W2021520922 @default.
- W4385737526 cites W2022050193 @default.
- W4385737526 cites W2025176940 @default.
- W4385737526 cites W2027785297 @default.
- W4385737526 cites W2028377933 @default.
- W4385737526 cites W2029667189 @default.
- W4385737526 cites W2033453768 @default.
- W4385737526 cites W2035353547 @default.
- W4385737526 cites W2036011280 @default.
- W4385737526 cites W2040650395 @default.
- W4385737526 cites W2040962503 @default.
- W4385737526 cites W2045104704 @default.
- W4385737526 cites W2054474037 @default.
- W4385737526 cites W2056040807 @default.
- W4385737526 cites W2057477511 @default.
- W4385737526 cites W2060079863 @default.
- W4385737526 cites W2063475539 @default.
- W4385737526 cites W2064056874 @default.
- W4385737526 cites W2067174909 @default.
- W4385737526 cites W2072285092 @default.
- W4385737526 cites W2075650606 @default.
- W4385737526 cites W2080107084 @default.
- W4385737526 cites W2081693079 @default.
- W4385737526 cites W2086292277 @default.
- W4385737526 cites W2086453930 @default.
- W4385737526 cites W2092537435 @default.
- W4385737526 cites W2094517081 @default.
- W4385737526 cites W2104316079 @default.
- W4385737526 cites W2105668062 @default.
- W4385737526 cites W2107029002 @default.
- W4385737526 cites W2109154308 @default.
- W4385737526 cites W2118362412 @default.
- W4385737526 cites W2119861196 @default.
- W4385737526 cites W2123511827 @default.
- W4385737526 cites W2125782175 @default.
- W4385737526 cites W2128963893 @default.
- W4385737526 cites W2130071037 @default.
- W4385737526 cites W2132262459 @default.
- W4385737526 cites W2132744522 @default.
- W4385737526 cites W2134967712 @default.
- W4385737526 cites W2136676465 @default.
- W4385737526 cites W2137372494 @default.
- W4385737526 cites W2137573895 @default.
- W4385737526 cites W2139173082 @default.
- W4385737526 cites W2144633939 @default.
- W4385737526 cites W2146544786 @default.
- W4385737526 cites W2150737519 @default.
- W4385737526 cites W2154046032 @default.
- W4385737526 cites W2157618287 @default.
- W4385737526 cites W2157760261 @default.
- W4385737526 cites W2164165466 @default.
- W4385737526 cites W2167279371 @default.
- W4385737526 cites W2168180694 @default.
- W4385737526 cites W2169878906 @default.
- W4385737526 cites W2206954826 @default.