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Caught in the act: how a brake on cell growth is anchored to lysosomes

Nature Structural & Molecular Biology volume 32, pages 2383–2384 (2025) Cite this article

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mTORC1 promotes cell growth by sensing nutrients and driving anabolic processes. When nutrients are scarce, GATOR1 turns off growth signals. Our study describes how KICSTOR links GATOR1 to lysosomes to enable its function, a finding that may help us to understand certain neurological disorders.

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Fig. 1: Integrated structural view of the KICSTOR–GATOR1–Rag–Ragulator supercomplex.
The alternative text for this image may have been generated using AI.

References

  1. Goul, C., Peruzzo, R. & Zoncu, R. The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease. Nat. Rev. Mol. Cell Biol. 12, 857–875 (2023). A review that provides structural and functional insights into the molecular architecture of mTORC1 regulators.

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  2. Wolfson, R. L. et al. KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1. Nature 543, 438–442 (2017). This paper reports that KICSTOR can serve as a scaffold to recruit GATOR1 to the lysosome.

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  3. Peng, M., Yin, N. & Li, M. O. SZT2 dictates GATOR control of mTORC1 signaling. Nature 543, 433–437 (2017). This paper reports that SZT2 has an essential role in regulating GATOR1 at the lysosome.

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  4. Su, M.-Y. et al. Cryo-EM structures of amino acid sensors bound to the human GATOR2 complex. Cell Rep. 44, 116088 (2025). This paper provides structural insights into the regulation of GATOR2 by amino acid sensors.

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This is a summary of: Teng, F. et al. Architecture of the human KICSTOR and GATOR1–KICSTOR complexes. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-025-01693-4 (2025).

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Caught in the act: how a brake on cell growth is anchored to lysosomes. Nat Struct Mol Biol 32, 2383–2384 (2025). https://doi.org/10.1038/s41594-025-01709-z

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