Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins

Macroautophagy is a cellular degradation process characterized by the formation of the double-membrane structure termed autophagosome (AP). The process of AP formation is not fully understood, but it is thought to happen through the combined action of direct lipid transfer and incorporation of new v...

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Autores: Varela, Yaiza R., Aguirre, Camila C., Iriondo, Marina N., Ballesteros, Uxue, Collado, M. Isabel, Etxaniz, Asier, Montes, L. Ruth, Goñi, Félix M., Alonso, Alicia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/399144
Acceso en línea:http://hdl.handle.net/10261/399144
https://api.elsevier.com/content/abstract/scopus_id/105011168729
Access Level:acceso abierto
Palabra clave:Autophagosome
Autophagy
Ceramide
LC3/GABARAP
Membrane fusion
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oai_identifier_str oai:digital.csic.es:10261/399144
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins
title Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins
spellingShingle Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins
Varela, Yaiza R.
Autophagosome
Autophagy
Ceramide
LC3/GABARAP
Membrane fusion
title_short Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins
title_full Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins
title_fullStr Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins
title_full_unstemmed Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins
title_sort Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteins
dc.creator.none.fl_str_mv Varela, Yaiza R.
Aguirre, Camila C.
Iriondo, Marina N.
Ballesteros, Uxue
Collado, M. Isabel
Etxaniz, Asier
Montes, L. Ruth
Goñi, Félix M.
Alonso, Alicia
author Varela, Yaiza R.
author_facet Varela, Yaiza R.
Aguirre, Camila C.
Iriondo, Marina N.
Ballesteros, Uxue
Collado, M. Isabel
Etxaniz, Asier
Montes, L. Ruth
Goñi, Félix M.
Alonso, Alicia
author_role author
author2 Aguirre, Camila C.
Iriondo, Marina N.
Ballesteros, Uxue
Collado, M. Isabel
Etxaniz, Asier
Montes, L. Ruth
Goñi, Félix M.
Alonso, Alicia
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Conferencia de Rectores de las Universidades Españolas
Consejo Superior de Investigaciones Científicas (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Commission
Eusko Jaurlaritza
Fundación Biofísica Bizkaia
Universidad del País Vasco
Varela, Yaiza R. [0000-0002-7601-4025]
Aguirre, Camila C. [0009-0003-3625-5531]
Iriondo, Marina N. [0000-0002-3816-0865]
Ballesteros, Uxue [0000-0001-8166-6485]
Collado, M. Isabel [0009-0004-8939-230X]
Etxaniz, Asier [0000-0003-2916-8256]
Montes, L. Ruth [0000-0002-4766-8417]
Goñi, Félix M. [0000-0001-6270-9216]
Alonso, Alicia [0000-0002-2730-7470]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Autophagosome
Autophagy
Ceramide
LC3/GABARAP
Membrane fusion
topic Autophagosome
Autophagy
Ceramide
LC3/GABARAP
Membrane fusion
description Macroautophagy is a cellular degradation process characterized by the formation of the double-membrane structure termed autophagosome (AP). The process of AP formation is not fully understood, but it is thought to happen through the combined action of direct lipid transfer and incorporation of new vesicles to the edges of the growing structure. Human LC3/GABARAP autophagy-related proteins are known to induce vesicle tethering and lipid mixing in vitro, which makes them suitable for the latter expansion mechanism. Ceramide (Cer) is a sphingolipid previously described to facilitate membrane fusion. Cer has also been related to macroautophagy modulation previously, although its specific role remains unclear. Moreover, the presence of sphingolipids in the AP has been suggested by recent experiments, increasing the relevance of Cer in macroautophagy. The present work has investigated the potential role that Cer could have on the proposed fusion of new vesicles to the nascent AP membrane. Interaction of purified ATG proteins with lipid vesicles of defined composition has been quantified using fluorescence spectroscopic techniques. Our results suggest that, if present, Cer could promote the vesicle tethering and leakage-free intervesicular lipid mixing induced by GABARAP and GABARAPL1, which would in turn mediate AP membrane expansion.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/399144
https://api.elsevier.com/content/abstract/scopus_id/105011168729
url http://hdl.handle.net/10261/399144
https://api.elsevier.com/content/abstract/scopus_id/105011168729
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124461NB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1007/s00018-025-05811-9
https://doi.org/10.1007/s00018-025-05811-9
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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repository.mail.fl_str_mv
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spelling Ceramide and the membrane-fusion activity of LC3/GABARAP autophagy proteinsVarela, Yaiza R.Aguirre, Camila C.Iriondo, Marina N.Ballesteros, UxueCollado, M. IsabelEtxaniz, AsierMontes, L. RuthGoñi, Félix M.Alonso, AliciaAutophagosomeAutophagyCeramideLC3/GABARAPMembrane fusionMacroautophagy is a cellular degradation process characterized by the formation of the double-membrane structure termed autophagosome (AP). The process of AP formation is not fully understood, but it is thought to happen through the combined action of direct lipid transfer and incorporation of new vesicles to the edges of the growing structure. Human LC3/GABARAP autophagy-related proteins are known to induce vesicle tethering and lipid mixing in vitro, which makes them suitable for the latter expansion mechanism. Ceramide (Cer) is a sphingolipid previously described to facilitate membrane fusion. Cer has also been related to macroautophagy modulation previously, although its specific role remains unclear. Moreover, the presence of sphingolipids in the AP has been suggested by recent experiments, increasing the relevance of Cer in macroautophagy. The present work has investigated the potential role that Cer could have on the proposed fusion of new vesicles to the nascent AP membrane. Interaction of purified ATG proteins with lipid vesicles of defined composition has been quantified using fluorescence spectroscopic techniques. Our results suggest that, if present, Cer could promote the vesicle tethering and leakage-free intervesicular lipid mixing induced by GABARAP and GABARAPL1, which would in turn mediate AP membrane expansion.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was funded in part by the Spanish Ministry of Science, Innovation, and Universities (MCIU), Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER) (grant No. PID2021-124461NB-I00), the Basque Government (grant No. IT1625-22), Fundación Biofísica Bizkaia, and the Basque Excellence Research Centre (BERC) program of the Basque Government and by the University of the Basque Country (grant No. EHU-N24/42). Y.R.V. and M.I.N. were recipients of predoctoral FPU fellowships from the Spanish Ministry of Science, Innovation and Universities (FPU18/00799, FPU16/05873); U.B. thanks the University of the Basque Country for a predoctoral contract (PIF19-152). C.C.A. was supported by a predoctoral contract from the Basque Government (PRE_2024_2_0086).Peer reviewedSpringer NatureConferencia de Rectores de las Universidades EspañolasConsejo Superior de Investigaciones Científicas (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)European CommissionEusko JaurlaritzaFundación Biofísica BizkaiaUniversidad del País VascoVarela, Yaiza R. [0000-0002-7601-4025]Aguirre, Camila C. [0009-0003-3625-5531]Iriondo, Marina N. [0000-0002-3816-0865]Ballesteros, Uxue [0000-0001-8166-6485]Collado, M. Isabel [0009-0004-8939-230X]Etxaniz, Asier [0000-0003-2916-8256]Montes, L. Ruth [0000-0002-4766-8417]Goñi, Félix M. [0000-0001-6270-9216]Alonso, Alicia [0000-0002-2730-7470]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/399144https://api.elsevier.com/content/abstract/scopus_id/105011168729reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124461NB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1007/s00018-025-05811-9https://doi.org/10.1007/s00018-025-05811-9Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3991442026-05-22T06:33:51Z
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