The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation

DC FieldValueLanguage
dc.contributor.authorCosentino, Katia
dc.contributor.authorHertlein, Vanessa
dc.contributor.authorJenner, Andreas
dc.contributor.authorDellmann, Timo
dc.contributor.authorGojkovic, Milos
dc.contributor.authorPena-Blanco, Aida
dc.contributor.authorDadsena, Shashank
dc.contributor.authorWajngarten, Noel
dc.contributor.authorDanial, John S. H.
dc.contributor.authorThevathasan, Jervis Vermal
dc.contributor.authorMund, Markus
dc.contributor.authorRies, Jonas
dc.contributor.authorGarcia-Saez, Ana J.
dc.date.accessioned2023-02-17T11:36:06Z-
dc.date.available2023-02-17T11:36:06Z-
dc.date.issued2022
dc.identifier.issn1097-2765
dc.identifier.urihttp://osnascholar.ub.uni-osnabrueck.de/handle/unios/65554-
dc.description.abstractBAX and BAK are key apoptosis regulators that mediate the decisive step of mitochondrial outer membrane permeabilization. However, the mechanism by which they assemble the apoptotic pore remains obscure. Here, we report that BAX and BAK present distinct oligomerization properties, with BAK organizing into smaller structures with faster kinetics than BAX. BAK recruits and accelerates BAX assembly into oligomers that continue to grow during apoptosis. As a result, BAX and BAK regulate each other as they co-assemble into the same apoptotic pores, which we visualize. The relative availability of BAX and BAK molecules thereby determines the growth rate of the apoptotic pore and the relative kinetics by which mitochondrial contents, most notably mtDNA, are released. This feature of BAX and BAK results in distinct activation kinetics of the cGAS/STING pathway with implications for mtDNA-mediated paracrine inflammatory signaling.
dc.description.sponsorshipEuropean Research Council [ERC-CoG 817758, ERC-CoG 724489]; Deutsche Forschungsgemeinschaft [CRC1403 project A02, CRC1218 project A09, GRK2364/1 MOMbrane]; Eliteprogramme for Postdocs of the Baden-WuEurorttemberg Stiftung; We thank Andreas Villunger for helpful discussions and Stephen Tait for providing SVEC cells. We thank Carolin StegmuEuroller for technical support. K.C. acknowledges the Eliteprogramme for Postdocs of the Baden-WuEurorttemberg Stiftung for financial support. This work was funded by the European Research Council (ERC-CoG 817758 to A.J.G.S. and ERC-CoG 724489 to J.R.) and partially supported by the Deutsche Forschungsgemeinschaft (CRC1403 project A02, CRC1218 project A09, and GRK2364/1 MOMbrane).
dc.language.isoen
dc.publisherCELL PRESS
dc.relation.ispartofMOLECULAR CELL
dc.subjectACTIVATION
dc.subjectBiochemistry & Molecular Biology
dc.subjectCell Biology
dc.subjectCELL-DEATH
dc.subjectMEMBRANE
dc.subjectOLIGOMERIZATION
dc.subjectPROAPOPTOTIC BAX
dc.subjectPROTEINS
dc.subjectSTANDARDS
dc.subjectVDAC2
dc.titleThe interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation
dc.typejournal article
dc.identifier.doi10.1016/j.molcel.2022.01.008
dc.identifier.isiISI:000765794000009
dc.description.volume82
dc.description.issue5
dc.description.startpage933+
dc.contributor.orcid0000-0002-3796-3500
dc.contributor.orcid0000-0002-8333-0712
dc.contributor.orcid0000-0003-3387-1120
dc.contributor.researcheridABG-8069-2020
dc.identifier.eissn1097-4164
dc.publisher.place50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
dcterms.isPartOf.abbreviationMol. Cell
dcterms.oaStatusGreen Published, hybrid
local.import.remainsaffiliations : Eberhard Karls University of Tubingen; University Osnabruck; University Osnabruck; University of Cologne; University of Cologne; European Molecular Biology Laboratory (EMBL)
local.import.remainsweb-of-science-index : Science Citation Index Expanded (SCI-EXPANDED)
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidCoKa893-
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