Logo do repositório
 
Publicação

Lipid unsaturation promotes BAX and BAK pore activity during apoptosis

2024-12Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorDadsena, Shashank
dc.contributor.authorCuevas Arenas, Rodrigo
dc.contributor.authorVieira, Gonçalo
dc.contributor.authorBrodesser, Susanne
dc.contributor.authorMelo, Manuel N.
dc.contributor.authorGarcía-Sáez, Ana J.
dc.contributor.institutionInstituto de Tecnologia Química e Biológica António Xavier (ITQB)
dc.contributor.pblNature Portfolio
dc.date.accessioned2025-05-07T21:18:44Z
dc.date.available2025-05-07T21:18:44Z
dc.date.issued2024-12
dc.descriptionFunding Information: This work was supported by European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation program (Grant agreement No. 817758), by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), SFB1218, project no. 269925409 and by CANTAR research network \u201CCANcer TARgeting\u201D, Ministry of Culture and Science of the State of Northrhine Westphalia, Germany and by FCT \u2013 Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia, I.P., through MOSTMICRO-ITQB R&D Unit (doi:10.54499/UIDB/04612/2020; doi:10.54499/UIDP/04612/2020), LS4FUTURE Associated Laboratory (doi:10.54499/LA/P/0087/2020) and CEECIND fellowship to M.N.M. (doi:10.54499/CEECIND/04124/2017/CP1428/CT0008). Special thanks to Prof. Christian Frezza and Dr. Nieves Peltzer for providing kidney and lung cancer cell lines. We thank Dr. R. Shalaby, Dr. H. Flores, Dr. L. Pedrera Puentes and Prof. A. Villunger for their technical input and stimulating discussions Publisher Copyright: © The Author(s) 2024.
dc.description.abstractBAX and BAK are proapoptotic members of the BCL2 family that directly mediate mitochondrial outer membrane permeabilition (MOMP), a central step in apoptosis execution. However, the molecular architecture of the mitochondrial apoptotic pore remains a key open question and especially little is known about the contribution of lipids to MOMP. By performing a comparative lipidomics analysis of the proximal membrane environment of BAK isolated in lipid nanodiscs, we find a significant enrichment of unsaturated species nearby BAK and BAX in apoptotic conditions. We then demonstrate that unsaturated lipids promote BAX pore activity in model membranes, isolated mitochondria and cellular systems, which is further supported by molecular dynamics simulations. Accordingly, the fatty acid desaturase FADS2 not only enhances apoptosis sensitivity, but also the activation of the cGAS/STING pathway downstream mtDNA release. The correlation of FADS2 levels with the sensitization to apoptosis of different lung and kidney cancer cell lines by co-treatment with unsaturated fatty acids supports the relevance of our findings. Altogether, our work provides an insight on how local lipid environment affects BAX and BAK function during apoptosis.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent5126912
dc.identifier.doi10.1038/s41467-024-49067-6
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 99520008
dc.identifier.otherPURE UUID: 0731476f-94a4-4470-b17f-f758fdd0eb29
dc.identifier.otherScopus: 85195000838
dc.identifier.otherPubMed: 38830851
dc.identifier.urihttp://hdl.handle.net/10362/182743
dc.identifier.urlhttps://www.scopus.com/pages/publications/85195000838
dc.language.isoeng
dc.peerreviewedyes
dc.subjectGeneral Chemistry
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.subjectGeneral Physics and Astronomy
dc.subjectSDG 3 - Good Health and Well-being
dc.titleLipid unsaturation promotes BAX and BAK pore activity during apoptosisen
dc.typejournal article
degois.publication.issue1
degois.publication.titleNature Communications
degois.publication.volume15
dspace.entity.typePublication
rcaap.rightsopenAccess

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
Lipid_unsaturation_promotes_BAX_and_BAK_pore_activity_during_apoptosis.pdf
Tamanho:
4.89 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

Home collection (ITQB)