Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair

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https://doi.org/10.48693/302
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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
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Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons