Home > Publications database > mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism. > print

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100 1 _ |a Levy, Tal
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245 _ _ |a mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism.
260 _ _ |a [London]
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|b Nature Publishing Group UK
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520 _ _ |a Energetic stress compels cells to evolve adaptive mechanisms to adjust their metabolism. Inhibition of mTOR kinase complex 1 (mTORC1) is essential for cell survival during glucose starvation. How mTORC1 controls cell viability during glucose starvation is not well understood. Here we show that the mTORC1 effectors eukaryotic initiation factor 4E binding proteins 1/2 (4EBP1/2) confer protection to mammalian cells and budding yeast under glucose starvation. Mechanistically, 4EBP1/2 promote NADPH homeostasis by preventing NADPH-consuming fatty acid synthesis via translational repression of Acetyl-CoA Carboxylase 1 (ACC1), thereby mitigating oxidative stress. This has important relevance for cancer, as oncogene-transformed cells and glioma cells exploit the 4EBP1/2 regulation of ACC1 expression and redox balance to combat energetic stress, thereby supporting transformation and tumorigenicity in vitro and in vivo. Clinically, high EIF4EBP1 expression is associated with poor outcomes in several cancer types. Our data reveal that the mTORC1-4EBP1/2 axis provokes a metabolic switch essential for survival during glucose starvation which is exploited by transformed and tumor cells.
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650 _ 2 |a Mechanistic Target of Rapamycin Complex 1: metabolism
|2 MeSH
650 _ 2 |a Mechanistic Target of Rapamycin Complex 1: genetics
|2 MeSH
650 _ 2 |a Glucose: metabolism
|2 MeSH
650 _ 2 |a Acetyl-CoA Carboxylase: metabolism
|2 MeSH
650 _ 2 |a Acetyl-CoA Carboxylase: genetics
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Adaptor Proteins, Signal Transducing: metabolism
|2 MeSH
650 _ 2 |a Adaptor Proteins, Signal Transducing: genetics
|2 MeSH
650 _ 2 |a Fatty Acids: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cell Survival
|2 MeSH
650 _ 2 |a Cell Cycle Proteins: metabolism
|2 MeSH
650 _ 2 |a Cell Cycle Proteins: genetics
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a NADP: metabolism
|2 MeSH
650 _ 2 |a Protein Biosynthesis
|2 MeSH
650 _ 2 |a Phosphoproteins: metabolism
|2 MeSH
650 _ 2 |a Phosphoproteins: genetics
|2 MeSH
650 _ 2 |a Oxidative Stress
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factors: metabolism
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factors: genetics
|2 MeSH
700 1 _ |a Voeltzke, Kai
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700 1 _ |a Hruby, Laura
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700 1 _ |a Alasad, Khawla
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700 1 _ |a Bas, Zuelal
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700 1 _ |a Vriens, Kim
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700 1 _ |a Stefanski, Anja
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700 1 _ |a Vargas-Toscano, Andres
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700 1 _ |a Kahlert, Ulf D
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700 1 _ |a Stühler, Kai
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700 1 _ |a Remke, Marc
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700 1 _ |a Elkabets, Moshe
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700 1 _ |a Grünewald, Thomas
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700 1 _ |a Reichert, Andreas S
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700 1 _ |a Fendt, Sarah-Maria
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700 1 _ |a Reifenberger, Guido
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700 1 _ |a Leprivier, Gabriel
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773 _ _ |a 10.1038/s41467-024-48386-y
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