DRP1 interacts directly with BAX to induce its activation and apoptosis.
BCL-2 proteins
fluorescence correlation spectroscopy
membrane protein complex
mitochondrial division
super-resolution microscopy
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
19 04 2022
19 04 2022
Historique:
revised:
01
12
2021
received:
27
04
2021
accepted:
03
12
2021
pubmed:
14
1
2022
medline:
21
4
2022
entrez:
13
1
2022
Statut:
ppublish
Résumé
The apoptotic executioner protein BAX and the dynamin-like protein DRP1 co-localize at mitochondria during apoptosis to mediate mitochondrial permeabilization and fragmentation. However, the molecular basis and functional consequences of this interplay remain unknown. Here, we show that BAX and DRP1 physically interact, and that this interaction is enhanced during apoptosis. Complex formation between BAX and DRP1 occurs exclusively in the membrane environment and requires the BAX N-terminal region, but also involves several other BAX surfaces. Furthermore, the association between BAX and DRP1 enhances the membrane activity of both proteins. Forced dimerization of BAX and DRP1 triggers their activation and translocation to mitochondria, where they induce mitochondrial remodeling and permeabilization to cause apoptosis even in the absence of apoptotic triggers. Based on this, we propose that DRP1 can promote apoptosis by acting as noncanonical direct activator of BAX through physical contacts with its N-terminal region.
Identifiants
pubmed: 35023587
doi: 10.15252/embj.2021108587
pmc: PMC9016351
doi:
Substances chimiques
bcl-2-Associated X Protein
0
Dynamins
EC 3.6.5.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e108587Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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