Lipids in Mitochondrial Macroautophagy: Phase Behavior of Bilayers Containing Cardiolipin and Ceramide
dc.contributor.author | Varela Fernández, Yaiza | |
dc.contributor.author | González Ramírez, Emilio José | |
dc.contributor.author | Iriondo Nagore, Marina | |
dc.contributor.author | Ballesteros Rivero, Uxue | |
dc.contributor.author | Etxaniz Iriondo, Asier | |
dc.contributor.author | Montes Burgos, Lidia Ruth | |
dc.contributor.author | Goñi Urcelay, Félix María | |
dc.contributor.author | Alonso Izquierdo, Alicia | |
dc.date.accessioned | 2023-03-31T13:31:34Z | |
dc.date.available | 2023-03-31T13:31:34Z | |
dc.date.issued | 2023-03-07 | |
dc.identifier.citation | International Journal of Molecular Sciences 24(6) : (2023) // Article ID 5080 | es_ES |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/10810/60582 | |
dc.description.abstract | Cardiolipin (CL) is a key lipid for damaged mitochondrial recognition by the LC3/GABARAP human autophagy proteins. The role of ceramide (Cer) in this process is unclear, but CL and Cer have been proposed to coexist in mitochondria under certain conditions. Varela et al. showed that in model membranes composed of egg sphingomyelin (eSM), dioleoyl phosphatidylethanolamine (DOPE), and CL, the addition of Cer enhanced the binding of LC3/GABARAP proteins to bilayers. Cer gave rise to lateral phase separation of Cer-rich rigid domains but protein binding took place mainly in the fluid continuous phase. In the present study, a biophysical analysis of bilayers composed of eSM, DOPE, CL, and/or Cer was attempted to understand the relevance of this lipid coexistence. Bilayers were studied by differential scanning calorimetry, confocal fluorescence microscopy, and atomic force microscopy. Upon the addition of CL and Cer, one continuous phase and two segregated ones were formed. In bilayers with egg phosphatidylcholine instead of eSM, in which the binding of LC3/GABARAP proteins hardly increased with Cer in the former study, a single segregated phase was formed. Assuming that phase separation at the nanoscale is ruled by the same principles acting at the micrometer scale, it is proposed that Cer-enriched rigid nanodomains, stabilized by eSM:Cer interactions formed within the DOPE- and CL-enriched fluid phase, result in structural defects at the rigid/fluid nanointerfaces, thus hypothetically facilitatingLC3/GABARAP protein interaction. | es_ES |
dc.description.sponsorship | 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 Ramón Areces (CIVP20A6619), Fundación Biofísica Bizkaia, and the Basque Excellence Research Centre (BERC) program of the Basque Government. E.J.G.-R. was supported by Fundación Ramón Areces. M.N.I. and Y.R.V. were recipients of pre-doctoral FPU fellowships from the Spanish Ministry of Science, Innovation, and Universities (FPU16/05873, FPU18/00799). U.B. thanks the University of the Basque Country for a pre-doctoral contract. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2021-124461NB-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | ceramide | es_ES |
dc.subject | cardiolipin | es_ES |
dc.subject | nanodomains | es_ES |
dc.subject | autophagy | es_ES |
dc.subject | LC3/GABARAP | es_ES |
dc.title | Lipids in Mitochondrial Macroautophagy: Phase Behavior of Bilayers Containing Cardiolipin and Ceramide | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2023-03-28T12:56:35Z | |
dc.rights.holder | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/24/6/5080 | es_ES |
dc.identifier.doi | 10.3390/ijms24065080 | |
dc.departamentoes | Bioquímica y biología molecular | |
dc.departamentoeu | Biokimika eta biologia molekularra |
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Except where otherwise noted, this item's license is described as © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).