Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol
Authors
King, L. E.Rodriguez-Enriquez, R.
Pedley, R.
Mellor, C. E. L.
Wang, Pengbo
Zindy, E.
White, M. R. H.
Brennan, K.
Gilmore, Andrew P
Affiliation
Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UKIssue Date
2022
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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.Citation
King 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.Journal
Cell Death and DifferentiationDOI
10.1038/s41418-022-01013-zPubMed ID
35585181Additional Links
https://dx.doi.org/10.1038/s41418-022-01013-zType
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41418-022-01013-z
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