DC Field | Value | Language |
dc.contributor.author | Dadsena, Shashank | |
dc.contributor.author | Bockelmann, Svenja | |
dc.contributor.author | Mina, John G. M. | |
dc.contributor.author | Hassan, Dina G. | |
dc.contributor.author | Korneev, Sergei | |
dc.contributor.author | Razzera, Guilherme | |
dc.contributor.author | Jahn, Helene | |
dc.contributor.author | Niekamp, Patrick | |
dc.contributor.author | Mueller, Dagmar | |
dc.contributor.author | Schneider, Markus | |
dc.contributor.author | Tafesse, Fikadu G. | |
dc.contributor.author | Marrink, Siewert J. | |
dc.contributor.author | Melo, Manuel N. | |
dc.contributor.author | Holthuis, Joost C. M. | |
dc.date.accessioned | 2021-12-23T16:23:47Z | - |
dc.date.available | 2021-12-23T16:23:47Z | - |
dc.date.issued | 2019 | |
dc.identifier.issn | 20411723 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/14662 | - |
dc.description.abstract | Ceramides draw wide attention as tumor suppressor lipids that act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are largely unknown. Using a photoactivatable ceramide probe, we here identify the voltage-dependent anion channels VDAC1 and VDAC2 as mitochondrial ceramide binding proteins. Coarse-grain molecular dynamics simulations reveal that both channels harbor a ceramide binding site on one side of the barrel wall. This site includes a membrane-buried glutamate that mediates direct contact with the ceramide head group. Substitution or chemical modification of this residue abolishes photolabeling of both channels with the ceramide probe. Unlike VDAC1 removal, loss of VDAC2 or replacing its membrane-facing glutamate with glutamine renders human colon cancer cells largely resistant to ceramide-induced apoptosis. Collectively, our data support a role of VDAC2 as direct effector of ceramide-mediated cell death, providing a molecular framework for how ceramides exert their anti-neoplastic activity. | |
dc.description.sponsorship | Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [SFB944-P14, HO3539/1-1]; Marie Curie Intra-European FellowshipEuropean Commission [289278]; German Egyptian Research Long-term Scholarship [57222240]; FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI) [LISBOA-01-0145-FEDER-007660]; FCT-Fundacao para a Ciencia e a TecnologiaPortuguese Foundation for Science and Technology; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R21AI124225-01A1]; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R21AI124225] Funding Source: NIH RePORTER; This work was supported by the Deutsche Forschungsgemeinschaft (Projects SFB944-P14 and HO3539/1-1) to J.C.M.H., a Marie Curie Intra-European Fellowship to J.G.M.M. (Project 289278), and a German Egyptian Research Long-term Scholarship to D.G.H. (Project 57222240). M.N.M was supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI) and by national funds through FCT-Fundacao para a Ciencia e a Tecnologia. M.N.M. and G.R. acknowledge the National Laboratory for Scientific Computing (LNCC/MCTI, Brazil) for providing HPC resources of the SDumont supercomputer (http://sdumont.lncc.br).Additional support was provided by the NIH (Project 1R21AI124225-01A1) to F.G.T. | |
dc.language.iso | en | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.relation.ispartof | NATURE COMMUNICATIONS | |
dc.subject | BAX | |
dc.subject | CELL-DEATH | |
dc.subject | DEPENDENT ANION CHANNEL-1 | |
dc.subject | EFFICIENT | |
dc.subject | INHIBITION | |
dc.subject | MEMBRANE | |
dc.subject | Multidisciplinary Sciences | |
dc.subject | PROTEINS | |
dc.subject | RADIATION-INDUCED APOPTOSIS | |
dc.subject | Science & Technology - Other Topics | |
dc.subject | SPHINGOLIPID METABOLISM | |
dc.subject | TRANSPORT | |
dc.title | Ceramides bind VDAC2 to trigger mitochondrial apoptosis | |
dc.type | journal article | |
dc.identifier.doi | 10.1038/s41467-019-09654-4 | |
dc.identifier.isi | ISI:000465200000013 | |
dc.description.volume | 10 | |
dc.contributor.orcid | 0000-0001-8423-5277 | |
dc.contributor.orcid | 0000-0003-0429-1370 | |
dc.contributor.orcid | 0000-0001-6567-0513 | |
dc.contributor.orcid | 0000-0002-2754-015X | |
dc.contributor.orcid | 0000-0002-0227-5900 | |
dc.contributor.orcid | 0000-0002-8575-4164 | |
dc.contributor.orcid | 0000-0001-8912-1586 | |
dc.contributor.researcherid | G-3706-2014 | |
dc.contributor.researcherid | N-8622-2014 | |
dc.contributor.researcherid | AAL-9157-2020 | |
dc.contributor.researcherid | AAX-9374-2021 | |
dc.contributor.researcherid | W-7033-2019 | |
dc.contributor.researcherid | AAG-2675-2021 | |
dc.publisher.place | MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND | |
dcterms.isPartOf.abbreviation | Nat. Commun. | |
dcterms.oaStatus | Green Published, gold | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | BoSv426 | - |
crisitem.author.netid | KoSe681 | - |