Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair
Please use this identifier to cite or link to this item:
https://doi.org/10.48693/302
https://doi.org/10.48693/302
Title: | Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair |
Authors: | 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 of the author: | 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 |
Abstract: | 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. |
Citations: | 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 |
Subject Keywords: | Calcium signalling; Lysosomes; Sphingolipids |
Issue Date: | 6-Apr-2022 |
License name: | Attribution 4.0 International |
License url: | http://creativecommons.org/licenses/by/4.0/ |
Type of publication: | Einzelbeitrag in einer wissenschaftlichen Zeitschrift [Article] |
Appears in Collections: | FB05 - Hochschulschriften Open-Access-Publikationsfonds |
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File | Description | Size | Format | |
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Niekamp_etal_naturecom_2022.pdf | Article | 4,5 MB | Adobe PDF | Niekamp_etal_naturecom_2022.pdf View/Open |
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