Universität zu Köln

Cosentino, Katia ORCID: 0000-0002-3796-3500, Hertlein, Vanessa, Jenner, Andreas, Dellmann, Timo, Gojkovic, Milos, Pena-Blanco, Aida, Dadsena, Shashank, Wajngarten, Noel ORCID: 0000-0003-3387-1120, Danial, John S. H., Thevathasan, Jervis Vermal, Mund, Markus, Ries, Jonas ORCID: 0000-0002-6640-9250 and Garcia-Saez, Ana J. (2022). The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation. Mol. Cell, 82 (5). S. 933 - 960. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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Abstract

BAX 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cosentino, Katia UNSPECIFIED orcid.org/0000-0002-3796-3500 UNSPECIFIED Hertlein, Vanessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Jenner, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dellmann, Timo UNSPECIFIED UNSPECIFIED UNSPECIFIED Gojkovic, Milos UNSPECIFIED UNSPECIFIED UNSPECIFIED Pena-Blanco, Aida UNSPECIFIED UNSPECIFIED UNSPECIFIED Dadsena, Shashank UNSPECIFIED UNSPECIFIED UNSPECIFIED Wajngarten, Noel UNSPECIFIED orcid.org/0000-0003-3387-1120 UNSPECIFIED Danial, John S. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevathasan, Jervis Vermal UNSPECIFIED UNSPECIFIED UNSPECIFIED Mund, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Ries, Jonas UNSPECIFIED orcid.org/0000-0002-6640-9250 UNSPECIFIED Garcia-Saez, Ana J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-678041
DOI:	10.1016/j.molcel.2022.01.008
Journal or Publication Title:	Mol. Cell
Volume:	82
Number:	5
Page Range:	S. 933 - 960
Date:	2022
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4164
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROAPOPTOTIC BAX; CELL-DEATH; MEMBRANE; PROTEINS; ACTIVATION; OLIGOMERIZATION; STANDARDS; VDAC2 Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67804