Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair
DC Element | Wert | Sprache |
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dc.contributor.author | Niekamp, Patrick | |
dc.contributor.author | Scharte, Felix | |
dc.contributor.author | Sokoya, Tolulope | |
dc.contributor.author | Vittadello, Laura | |
dc.contributor.author | Kim, Yeongho | |
dc.contributor.author | Deng, Yongqiang | |
dc.contributor.author | Sudhoff, Elisabeth | |
dc.contributor.author | Hilderink, Angelika | |
dc.contributor.author | Imlau, Mirco | |
dc.contributor.author | Clarke, Christopher J. | |
dc.contributor.author | Hensel, Michael | |
dc.contributor.author | Burd, Christopher G. | |
dc.contributor.author | Holthuis, Joost C. M. | |
dc.date.accessioned | 2024-01-04T10:37:19Z | - |
dc.date.available | 2024-01-04T10:37:19Z | - |
dc.date.issued | 2022 | |
dc.identifier.uri | http://osnascholar.ub.uni-osnabrueck.de/handle/unios/73272 | - |
dc.description.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. Activation of ESCRT prevents potentially lethal outcomes of minor perturbations in lysosomal integrity. Here authors show that Ca2 -activated scrambling of sphingomyelin and its cytosolic turnover drives lysosomal repair independently of ESCRT. | |
dc.description.sponsorship | Deutsche Forschungsgemeinschaft [SFB944-P14, HO3539/1-1, SFB944-P4, SPP-2225 HE1964/23-1, INST 901/179]; National Institute of General Medical Sciences of the United States National Institutes of Health [R01GM095766]; We gratefully acknowledge Caroline Barisch, Anthony Hyman, and Yusuf Hannun for providing DNA constructs, cell lines, and bacterial strains, Florian Frohlich and Stefan Walter for technical support in LC-MS, and Rainer Kurre for technical support in live-cell microscopy. This work was supported by the Deutsche Forschungsgemeinschaft (projects SFB944-P14 and HO3539/1-1 to J.C.M.H., SFB944-P4 and SPP-2225 HE1964/23-1 to M.H., and INST 901/179 to M.I.) as well as by the National Institute of General Medical Sciences of the United States National Institutes of Health (award R01GM095766 to C.G.B.). | |
dc.language.iso | en | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | NATURE COMMUNICATIONS | |
dc.subject | AUTOPHAGY | |
dc.subject | CELL-MEMBRANE | |
dc.subject | CERAMIDE | |
dc.subject | CYTOSOL | |
dc.subject | DEATH | |
dc.subject | GOLGI | |
dc.subject | Multidisciplinary Sciences | |
dc.subject | PLASMA-MEMBRANE | |
dc.subject | PROTEIN | |
dc.subject | Science & Technology - Other Topics | |
dc.subject | VESICLES | |
dc.title | Ca<SUP>2+</SUP>-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair | |
dc.type | journal article | |
dc.identifier.doi | 10.1038/s41467-022-29481-4 | |
dc.identifier.isi | ISI:000779311200038 | |
dc.description.volume | 13 | |
dc.description.issue | 1 | |
dc.contributor.orcid | https://orcid.org/0000-0002-1477-925X | |
dc.contributor.orcid | https://orcid.org/0000-0002-6710-9524 | |
dc.contributor.orcid | https://orcid.org/0000-0001-6604-6253 | |
dc.contributor.orcid | https://orcid.org/0000-0001-5112-9128 | |
dc.contributor.orcid | https://orcid.org/0000-0001-8912-1586 | |
dc.contributor.orcid | https://orcid.org/0000-0002-4855-522X | |
dc.contributor.orcid | https://orcid.org/0000-0001-8023-0946 | |
dc.contributor.researcherid | G-2978-2018 | |
dc.identifier.eissn | 2041-1723 | |
dc.publisher.place | HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY | |
dcterms.isPartOf.abbreviation | Nat. Commun. | |
dcterms.oaStatus | Green Submitted, Green Published, gold | |
local.import.remains | affiliations : University Osnabruck; University Osnabruck; University Osnabruck; University Osnabruck; Yale University; State University of New York (SUNY) System; State University of New York (SUNY) Stony Brook; State University of New York (SUNY) System; State University of New York (SUNY) Stony Brook | |
local.import.remains | web-of-science-index : Science Citation Index Expanded (SCI-EXPANDED) | |
crisitem.author.dept | FB 04 - Physik | - |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb04 | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-5343-5636 | - |
crisitem.author.orcid | 0000-0001-6604-6253 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | ImMi360 | - |
crisitem.author.netid | HeMi480 | - |
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geprüft am 19.05.2024