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The minimal membrane requirements for BAX-induced pore opening upon exposure to oxidative stress

dc.contributor.authorMystek, Paweł
dc.contributor.authorSingh, Vandana
dc.contributor.authorHorváth, Matěj
dc.contributor.authorHonzejková, Karolína
dc.contributor.authorRiegerová, Petra
dc.contributor.authorEvci, Hüseyin
dc.contributor.authorHof, Martin
dc.contributor.authorObšil, Tomáš
dc.contributor.authorŠachl, Radek
dc.date.accessioned2025-03-03T06:13:04Z
dc.date.available2025-03-03T06:13:04Z
dc.date.issued2024
dc.identifier.urihttps://hdl.handle.net/20.500.14178/2945
dc.description.abstractPerforation of the outer mitochondrial membrane triggered by BAX and facilitated by its main activator cBID is a fundamental process in cell apoptosis. Here, we employ a newly designed correlative approach based on a combination of a fluorescence cross correlation binding with a calcein permeabilization assay to understand the involvement of BAX in pore formation under oxidative stress conditions. To mimic the oxidative stress, we enriched liposomal membranes by phosphatidylcholines with truncated sn-2 acyl chains terminated by a carboxyl or aldehyde moiety. Our observations revealed that oxidative stress enhances proapoptotic conditions involving accelerated pore-opening kinetics. This enhancement is achieved through increased recruitment of BAX to the membrane and facilitation of BAX membrane insertion. Despite these effects, the fundamental mechanism of pore formation remained unchanged, suggesting an all-or-none mechanism. In line with this mechanism, we demonstrated that the minimal number of BAX molecules at the membrane necessary for pore formation remains constant regardless of BAX activation by cBID or the presence of oxidized lipids. Overall, our findings give a comprehensive picture of the molecular mechanisms underlying apoptotic pore formation and highlight the selective amplifying role of oxidized lipids in triggering formation of membrane pores.en
dc.language.isoen
dc.relation.urlhttps://doi.org/10.1016/j.bpj.2024.08.017
dc.rightsCreative Commons Uveďte původ-Neužívejte dílo komerčně-Nezpracovávejte 4.0 Internationalcs
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivativeWorks 4.0 Internationalen
dc.titleThe minimal membrane requirements for BAX-induced pore opening upon exposure to oxidative stressen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
dc.date.updated2025-03-03T06:13:04Z
dc.subject.keywordBAXen
dc.subject.keywordcBIDen
dc.subject.keywordapoptosisen
dc.subject.keywordouter mitochondrial membrane (OMM)en
dc.subject.keywordpore formationen
dc.subject.keywordoxidative stressen
dc.subject.keywordmembrane permeabilizationen
dc.subject.keywordfluorescence cross-correlation bindingen
dc.subject.keywordcalcein permeabilization assayen
dc.subject.keywordproapoptotic conditionsen
dc.subject.keywordBAX membrane insertionen
dc.subject.keywordoxidized lipiden
dc.identifier.eissn1542-0086
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/GAUK/GAUK1160120
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/COOP/COOP
dc.date.embargoStartDate2025-03-03
dc.type.obd73
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.bpj.2024.08.017
dc.identifier.utWos001389451300001
dc.identifier.eidScopus2-s2.0-85206708095
dc.identifier.obd652199
dc.identifier.pubmed39188056
dc.subject.rivPrimary10000::10300::10301
dc.subject.rivSecondary10000::10400::10403
dcterms.isPartOf.nameBiophysical Journal
dcterms.isPartOf.issn0006-3495
dcterms.isPartOf.journalYear2024
dcterms.isPartOf.journalVolume123
dcterms.isPartOf.journalIssue20
uk.faculty.primaryId116
uk.faculty.primaryNameMatematicko-fyzikální fakultacs
uk.faculty.primaryNameFaculty of Mathematics and Physicsen
uk.faculty.secondaryId115
uk.faculty.secondaryNamePřírodovědecká fakultacs
uk.faculty.secondaryNameFaculty of Scienceen
uk.department.primaryId1191
uk.department.primaryNameFyzikální ústav UKcs
uk.department.primaryNameInstitute of Physics of Charles Universityen
uk.department.secondaryId1049
uk.department.secondaryNameKatedra fyzikální a makromolekulární chemiecs
uk.department.secondaryNameDepartment of Physical and Macromolecular Chemistryen
dc.description.pageRange3519-3532
dc.type.obdHierarchyCsČLÁNEK V ČASOPISU::článek v časopisu::původní článekcs
dc.type.obdHierarchyEnJOURNAL ARTICLE::journal article::original articleen
dc.type.obdHierarchyCode73::152::206en
uk.displayTitleThe minimal membrane requirements for BAX-induced pore opening upon exposure to oxidative stressen


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