Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol.
Cell Death Differ
; 29(11): 2262-2274, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35585181
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-bcl-2
/
Mitocôndrias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido