Lipid unsaturation promotes BAX and BAK pore activity during apoptosis

Bibliographic Details
Main Author: Dadsena, Shashank
Publication Date: 2024
Other Authors: Cuevas Arenas, Rodrigo, Vieira, Gonçalo, Brodesser, Susanne, Melo, Manuel N., García-Sáez, Ana J.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/182743
Summary: Funding 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.
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spelling Lipid unsaturation promotes BAX and BAK pore activity during apoptosisChemistry(all)Biochemistry, Genetics and Molecular Biology(all)Physics and Astronomy(all)SDG 3 - Good Health and Well-beingFunding 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.BAX 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.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNDadsena, ShashankCuevas Arenas, RodrigoVieira, GonçaloBrodesser, SusanneMelo, Manuel N.García-Sáez, Ana J.2025-05-07T21:18:44Z2024-122024-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/182743eng2041-1723PURE: 99520008https://doi.org/10.1038/s41467-024-49067-6info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-05-19T01:39:21Zoai:run.unl.pt:10362/182743Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T07:13:46.559991Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Lipid unsaturation promotes BAX and BAK pore activity during apoptosis
title Lipid unsaturation promotes BAX and BAK pore activity during apoptosis
spellingShingle Lipid unsaturation promotes BAX and BAK pore activity during apoptosis
Dadsena, Shashank
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
SDG 3 - Good Health and Well-being
title_short Lipid unsaturation promotes BAX and BAK pore activity during apoptosis
title_full Lipid unsaturation promotes BAX and BAK pore activity during apoptosis
title_fullStr Lipid unsaturation promotes BAX and BAK pore activity during apoptosis
title_full_unstemmed Lipid unsaturation promotes BAX and BAK pore activity during apoptosis
title_sort Lipid unsaturation promotes BAX and BAK pore activity during apoptosis
author Dadsena, Shashank
author_facet Dadsena, Shashank
Cuevas Arenas, Rodrigo
Vieira, Gonçalo
Brodesser, Susanne
Melo, Manuel N.
García-Sáez, Ana J.
author_role author
author2 Cuevas Arenas, Rodrigo
Vieira, Gonçalo
Brodesser, Susanne
Melo, Manuel N.
García-Sáez, Ana J.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Dadsena, Shashank
Cuevas Arenas, Rodrigo
Vieira, Gonçalo
Brodesser, Susanne
Melo, Manuel N.
García-Sáez, Ana J.
dc.subject.por.fl_str_mv Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
SDG 3 - Good Health and Well-being
topic Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
SDG 3 - Good Health and Well-being
description Funding 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.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
2024-12-01T00:00:00Z
2025-05-07T21:18:44Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/182743
url http://hdl.handle.net/10362/182743
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2041-1723
PURE: 99520008
https://doi.org/10.1038/s41467-024-49067-6
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
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reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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