ArticleNature cell biology2023
Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor.
Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Metabolic engineering and adaptive laboratory evolution enhance squalene production inSynthetic and systems biotechnology · 2026Article
- Gut‑bone metabolites: SCFAs, polyamines and microbial metabolomics in osteoporosis risk and therapy (Review).International journal of molecular medicine · 2026Review
- Article
- GRASP55 maintains lysosome function by controlling sorting of lysosomal enzymes at the Golgi.EMBO reports · 2026Article
- Fatty acid synthesis supports tumor progression through facilitating the activity of TORC1 signaling.Cell death & disease · 2026Article
- Malonyl-CoA Decarboxylase: A Spotlight on Brain Aspects.Brain sciences · 2026Review
- MCD enzyme deficiency drives early mortality and multiorgan metabolic disruption in Dahl salt-sensitive rats.iScience · 2026Article
- Acetyl-CoA carboxylase maintains energetic balance for functional oogenesis.Nature communications · 2025Article
- Solar-hybrid biocatalyst for methane hydroxylation to methanol.Nature communications · 2025Article
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- The tumor suppressor CYLD acts as a deubiquitinase for mTOR to constrain its activity.bioRxiv : the preprint server for biology · 2025Article
- Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies.Cell communication and signaling : CCS · 2025Review
- On the pixel selection criterion for the calculation of the Pearson's correlation coefficient in fluorescence microscopy.Journal of microscopy · 2025Article
- A Genetically Encoded Fluorescent Biosensor for Intracellular Measurement of Malonyl-CoA.ACS bio & med chem Au · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- Spatial and functional separation of mTORC1 signalling in response to different amino acid sources.Nature cell biology · 2024Article
- A Genetically Encoded Fluorescent Biosensor for Intracellular Measurement of Malonyl-CoA.bioRxiv : the preprint server for biology · 2024Article
- Emerging targets in lipid metabolism for cancer therapy.Trends in pharmacological sciences · 2024Review
- A fast-acting lipid checkpoint in G1 prevents mitotic defects.Nature communications · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.