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Stress granules plug and stabilize damaged endolysosomal membranes

Author

Listed:
  • Claudio Bussi

    (The Francis Crick Institute)

  • Agustín Mangiarotti

    (Max Planck Institute of Colloids and Interfaces)

  • Christian Vanhille-Campos

    (Institute of Science and Technology Austria
    University College London)

  • Beren Aylan

    (The Francis Crick Institute)

  • Enrica Pellegrino

    (The Francis Crick Institute)

  • Natalia Athanasiadi

    (The Francis Crick Institute)

  • Antony Fearns

    (The Francis Crick Institute)

  • Angela Rodgers

    (The Francis Crick Institute)

  • Titus M. Franzmann

    (Technische Universität Dresden)

  • Anđela Šarić

    (Institute of Science and Technology Austria)

  • Rumiana Dimova

    (Max Planck Institute of Colloids and Interfaces)

  • Maximiliano G. Gutierrez

    (The Francis Crick Institute)

Abstract

Endomembrane damage represents a form of stress that is detrimental for eukaryotic cells1,2. To cope with this threat, cells possess mechanisms that repair the damage and restore cellular homeostasis3–7. Endomembrane damage also results in organelle instability and the mechanisms by which cells stabilize damaged endomembranes to enable membrane repair remains unknown. Here, by combining in vitro and in cellulo studies with computational modelling we uncover a biological function for stress granules whereby these biomolecular condensates form rapidly at endomembrane damage sites and act as a plug that stabilizes the ruptured membrane. Functionally, we demonstrate that stress granule formation and membrane stabilization enable efficient repair of damaged endolysosomes, through both ESCRT (endosomal sorting complex required for transport)-dependent and independent mechanisms. We also show that blocking stress granule formation in human macrophages creates a permissive environment for Mycobacterium tuberculosis, a human pathogen that exploits endomembrane damage to survive within the host.

Suggested Citation

  • Claudio Bussi & Agustín Mangiarotti & Christian Vanhille-Campos & Beren Aylan & Enrica Pellegrino & Natalia Athanasiadi & Antony Fearns & Angela Rodgers & Titus M. Franzmann & Anđela Šarić & Rumiana D, 2023. "Stress granules plug and stabilize damaged endolysosomal membranes," Nature, Nature, vol. 623(7989), pages 1062-1069, November.
  • Handle: RePEc:nat:nature:v:623:y:2023:i:7989:d:10.1038_s41586-023-06726-w
    DOI: 10.1038/s41586-023-06726-w
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