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Lysosomal recruitment of TSC2 is a universal response to cellular stress

Author

Listed:
  • Constantinos Demetriades

    (German Cancer Research Center (DKFZ))

  • Monika Plescher

    (German Cancer Research Center (DKFZ))

  • Aurelio A. Teleman

    (German Cancer Research Center (DKFZ))

Abstract

mTORC1 promotes cell growth and is therefore inactivated upon unfavourable growth conditions. Signalling pathways downstream of most cellular stresses converge on TSC1/2, which serves as an integration point that inhibits mTORC1. The TSC1/2 complex was shown to translocate to lysosomes to inactivate mTORC1 in response to two stresses: amino-acid starvation and growth factor removal. Whether other stresses also regulate TSC2 localization is not known. How TSC2 localization responds to combinations of stresses and other stimuli is also unknown. We show that both amino acids and growth factors are required simultaneously to maintain TSC2 cytoplasmic; when one of the two is missing, TSC2 relocalizes to lysosomes. Furthermore, multiple different stresses that inhibit mTORC1 also drive TSC2 lysosomal accumulation. Our findings indicate that lysosomal recruitment of TSC2 is a universal response to stimuli that inactivate mTORC1, and that the presence of any single stress is sufficient to cause TSC2 lysosomal localization.

Suggested Citation

  • Constantinos Demetriades & Monika Plescher & Aurelio A. Teleman, 2016. "Lysosomal recruitment of TSC2 is a universal response to cellular stress," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10662
    DOI: 10.1038/ncomms10662
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    Cited by:

    1. Mykola Roiuk & Marilena Neff & Aurelio A. Teleman, 2024. "eIF4E-independent translation is largely eIF3d-dependent," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Ana Belén Plata-Gómez & Lucía Prado-Rivas & Alba Sanz & Nerea Deleyto-Seldas & Fernando García & Celia Calle Arregui & Camila Silva & Eduardo Caleiras & Osvaldo Graña-Castro & Elena Piñeiro-Yáñez & Jo, 2024. "Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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