Universität zu Köln

King, Louise E., Rodriguez-Enriquez, Ricardo, Pedley, Robert ORCID: 0000-0002-0801-7240, Mellor, Charlotte E. L., Wang, Pengbo, Zindy, Egor ORCID: 0000-0003-0033-0002, White, Michael R. H., Brennan, Keith ORCID: 0000-0002-9384-125X and Gilmore, Andrew P. (2022). Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol. Cell Death Differ., 29 (11). S. 2262 - 2275. LONDON: SPRINGERNATURE. ISSN 1476-5403

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Abstract

Apoptosis is regulated by interactions between the BH3-only and multi-domain Bcl-2 family proteins. These interactions are integrated on the outer mitochondrial membrane (OMM) where they set the threshold for apoptosis, known as mitochondrial priming. However, how mitochondrial priming is controlled at the level of single cells remains unclear. Retrotranslocation of Bcl-XL has been proposed as one mechanism, removing pro-apoptotic Bcl-2 proteins from the OMM, thus reducing priming. Contrary to this view, we now show that Bcl-XL retrotranslocation is inhibited by binding to its BH3-only partners, resulting in accumulation of these protein complexes on mitochondria. We find that Bcl-XL retrotranslocation dynamics are tightly coupled to mitochondrial priming. Quantifying these dynamics indicates the heterogeneity in priming between cells within a population and predicts how they subsequently respond to a pro-apoptotic signal.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code King, Louise E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rodriguez-Enriquez, Ricardo UNSPECIFIED UNSPECIFIED UNSPECIFIED Pedley, Robert UNSPECIFIED orcid.org/0000-0002-0801-7240 UNSPECIFIED Mellor, Charlotte E. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Pengbo UNSPECIFIED UNSPECIFIED UNSPECIFIED Zindy, Egor UNSPECIFIED orcid.org/0000-0003-0033-0002 UNSPECIFIED White, Michael R. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brennan, Keith UNSPECIFIED orcid.org/0000-0002-9384-125X UNSPECIFIED Gilmore, Andrew P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-680868
DOI:	10.1038/s41418-022-01013-z
Journal or Publication Title:	Cell Death Differ.
Volume:	29
Number:	11
Page Range:	S. 2262 - 2275
Date:	2022
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1476-5403
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BH3-ONLY PROTEINS; BH3 PROTEINS; BAX; FAMILY; DEATH; BINDING; CANCER; BCL-X(L); XL; INHIBITION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68086