Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol
AuthorsKing, L. E.
Mellor, C. E. L.
White, M. R. H.
Gilmore, Andrew P
AffiliationWellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK
MetadataShow full item record
AbstractApoptosis 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.
CitationKing LE, Rodriguez-Enriquez R, Pedley R, Mellor CEL, Wang P, Zindy E, et al. Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol. Cell Death & Differentiation. Springer Science and Business Media LLC; 2022.
JournalCell Death and Differentiation
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