Stress granules plug and stabilize damaged endolysosomal membranes
Bussi C, Mangiarotti A, Vanhille-Campos CE, Aylan B, Pellegrino E, Athanasiadi N, Fearns A, Rodgers A, Franzmann TM, Šarić A, Dimova R, Gutierrez MG. 2023. Stress granules plug and stabilize damaged endolysosomal membranes. Nature.
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Author
Bussi, Claudio;
Mangiarotti, Agustín;
Vanhille-Campos, Christian EduardoISTA;
Aylan, Beren;
Pellegrino, Enrica;
Athanasiadi, Natalia;
Fearns, Antony;
Rodgers, Angela;
Franzmann, Titus M.;
Šarić, AnđelaISTA 
;
Dimova, Rumiana;
Gutierrez, Maximiliano G.
All
;
Dimova, Rumiana;
Gutierrez, Maximiliano G.
All
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Abstract
<jats:title>Abstract</jats:title><jats:p>Endomembrane damage represents a form of stress that is detrimental for eukaryotic cells<jats:sup>1,2</jats:sup>. To cope with this threat, cells possess mechanisms that repair the damage and restore cellular homeostasis<jats:sup>3–7</jats:sup>. 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 <jats:italic>Mycobacterium tuberculosis</jats:italic>, a human pathogen that exploits endomembrane damage to survive within the host.</jats:p>
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Date Published
2023-11-15
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Nature
Acknowledgement
We thank the Human Embryonic Stem Cell Unit, Advanced Light Microscopy and High-throughput Screening facilities at the Crick for their support in various aspects of the work. We thank the laboratory of P. Anderson for providing the G3BP-DKO U2OS cells. The authors thank N. Chen for providing the purified glycinin protein; Z. Zhao for providing the microfluidic chip wafers; and M. Amaral and F. Frey for helpful discussions and valuable input regarding analysis methods. This work was supported by the Francis Crick Institute (to M.G.G.), which receives its core funding from Cancer Research UK (FC001092), the UK Medical Research Council (FC001092) and the Wellcome Trust (FC001092). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 772022 to M.G.G.). C.B. has received funding from the European Respiratory Society and the European Union’s H2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 713406. A.M. acknowledges support from Alexander von Humboldt Foundation and C.V.-C. acknowledges funding by the Royal Society and the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant no. 802960 to A.S.). All simulations were carried out on the high-performance computing cluster at the Institute of Science and Technology Austria. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Open Access funding provided by The Francis Crick Institute.
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Cite this
Bussi C, Mangiarotti A, Vanhille-Campos CE, et al. Stress granules plug and stabilize damaged endolysosomal membranes. Nature. 2023. doi:10.1038/s41586-023-06726-w
Bussi, C., Mangiarotti, A., Vanhille-Campos, C. E., Aylan, B., Pellegrino, E., Athanasiadi, N., … Gutierrez, M. G. (2023). Stress granules plug and stabilize damaged endolysosomal membranes. Nature. Springer Nature. https://doi.org/10.1038/s41586-023-06726-w
Bussi, Claudio, Agustín Mangiarotti, Christian Eduardo Vanhille-Campos, Beren Aylan, Enrica Pellegrino, Natalia Athanasiadi, Antony Fearns, et al. “Stress Granules Plug and Stabilize Damaged Endolysosomal Membranes.” Nature. Springer Nature, 2023. https://doi.org/10.1038/s41586-023-06726-w.
C. Bussi et al., “Stress granules plug and stabilize damaged endolysosomal membranes,” Nature. Springer Nature, 2023.
Bussi C, Mangiarotti A, Vanhille-Campos CE, Aylan B, Pellegrino E, Athanasiadi N, Fearns A, Rodgers A, Franzmann TM, Šarić A, Dimova R, Gutierrez MG. 2023. Stress granules plug and stabilize damaged endolysosomal membranes. Nature.
Bussi, Claudio, et al. “Stress Granules Plug and Stabilize Damaged Endolysosomal Membranes.” Nature, Springer Nature, 2023, doi:10.1038/s41586-023-06726-w.
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