Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol
Year: 2022
Type: article
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.
Source: Cell Death and Differentiation
Institutions: University of Cologne, Wellcome Centre for Cell-Matrix Research, University of Manchester, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, St. Jude Children's Research Hospital, Cancer Research UK Manchester Institute, Université Libre de Bruxelles, Manchester Academic Health Science Centre
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,290
Awards: Regenerative medicine: instrumentation for flow cytometry and cell printing, Wellcome Trust Centre for Cell-Matrix Research core award renewal., Wellcome Trust Centre for Cell-Matrix Research core award renewal., Institutional Strategic Support Fund, Institutional Strategic Support Fund, G8670372459, G8951412869, G9000182122
OpenAlex ID: W4280608246