Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair
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https://doi.org/10.48693/302
https://doi.org/10.48693/302
Titel: | Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair |
Autor(en): | Niekamp, Patrick Felix, Scharte Tolulope, Sokoya Vittadello, Laura Kim, Yeongho Deng, Yongqiang Südhoff, Elisabeth Hilderink, Angelika Imlau, Mirco Clarke, Christopher J. Hensel, Michael Burd, Christopher G. Holthuis, Joost C. M. |
ORCID des Autors: | https://orcid.org/0000-0001-8023-0946 https://orcid.org/0000-0002-6710-9524 https://orcid.org/0000-0001-8912-1586 https://orcid.org/0000-0002-4855-522X https://orcid.org/0000-0002-1477-925X |
Zusammenfassung: | Lysosomes are vital organelles vulnerable to injuries from diverse materials. Failure to repair or sequester damaged lysosomes poses a threat to cell viability. Here we report that cells exploit a sphingomyelin-based lysosomal repair pathway that operates independently of ESCRT to reverse potentially lethal membrane damage. Various conditions perturbing organelle integrity trigger a rapid calcium-activated scrambling and cytosolic exposure of sphingomyelin. Subsequent metabolic conversion of sphingomyelin by neutral sphingomyelinases on the cytosolic surface of injured lysosomes promotes their repair, also when ESCRT function is compromised. Conversely, blocking turnover of cytosolic sphingomyelin renders cells more sensitive to lysosome-damaging drugs. Our data indicate that calcium-activated scramblases, sphingomyelin, and neutral sphingomyelinases are core components of a previously unrecognized membrane restoration pathway by which cells preserve the functional integrity of lysosomes. |
Bibliografische Angaben: | Niekamp, P., Scharte, F., Sokoya, T., Vittadello, L., Kim, Y., Deng, Y., . . . Holthuis, J. C. M. (2022): Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair. Nature Communications, 13(1), 1875. |
URL: | https://doi.org/10.48693/302 https://osnadocs.ub.uni-osnabrueck.de/handle/ds-202305028771 |
Schlagworte: | Calcium signalling; Lysosomes; Sphingolipids |
Erscheinungsdatum: | 6-Apr-2022 |
Lizenzbezeichnung: | Attribution 4.0 International |
URL der Lizenz: | http://creativecommons.org/licenses/by/4.0/ |
Publikationstyp: | Einzelbeitrag in einer wissenschaftlichen Zeitschrift [Article] |
Enthalten in den Sammlungen: | FB05 - Hochschulschriften Open-Access-Publikationsfonds |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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Niekamp_etal_naturecom_2022.pdf | Article | 4,5 MB | Adobe PDF | Niekamp_etal_naturecom_2022.pdf Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons