BCL-2-family protein tBID can act as a BAX-like effector of apoptosis.
Apoptosis
Apoptosis Regulatory Proteins
/ metabolism
BH3 Interacting Domain Death Agonist Protein
/ chemistry
HCT116 Cells
HeLa Cells
Humans
Mitochondria
/ metabolism
Mitochondrial Proteins
/ metabolism
Protein Domains
Proteolysis
Proto-Oncogene Proteins c-bcl-2
/ metabolism
bcl-2 Homologous Antagonist-Killer Protein
/ metabolism
bcl-2-Associated X Protein
/ metabolism
BCL-2 proteins
apoptosis
mitochondrial permeabilization
pore formation
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
17 12 2022
17 12 2022
Historique:
revised:
14
11
2021
received:
10
05
2021
accepted:
22
11
2021
pubmed:
22
12
2021
medline:
17
2
2022
entrez:
21
12
2021
Statut:
ppublish
Résumé
During apoptosis, the BCL-2-family protein tBID promotes mitochondrial permeabilization by activating BAX and BAK and by blocking anti-apoptotic BCL-2 members. Here, we report that tBID can also mediate mitochondrial permeabilization by itself, resulting in release of cytochrome c and mitochondrial DNA, caspase activation and apoptosis even in absence of BAX and BAK. This previously unrecognized activity of tBID depends on helix 6, homologous to the pore-forming regions of BAX and BAK, and can be blocked by pro-survival BCL-2 proteins. Importantly, tBID-mediated mitochondrial permeabilization independent of BAX and BAK is physiologically relevant for SMAC release in the immune response against Shigella infection. Furthermore, it can be exploited to kill leukaemia cells with acquired venetoclax resistance due to lack of active BAX and BAK. Our findings define tBID as an effector of mitochondrial permeabilization in apoptosis and provide a new paradigm for BCL-2 proteins, with implications for anti-bacterial immunity and cancer therapy.
Identifiants
pubmed: 34931711
doi: 10.15252/embj.2021108690
pmc: PMC8762556
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
BAK1 protein, human
0
BCL2 protein, human
0
BH3 Interacting Domain Death Agonist Protein
0
DIABLO protein, human
0
Mitochondrial Proteins
0
Proto-Oncogene Proteins c-bcl-2
0
bcl-2 Homologous Antagonist-Killer Protein
0
bcl-2-Associated X Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e108690Informations de copyright
© 2021 The Authors Published under the terms of the CC BY 4.0 license.
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