Jenner, Andreas, Pena-Blanco, Aida, Salvador-Gallego, Raquel, Ugarte-Uribe, Begona, Zollo, Cristiana, Ganief, Tariq, Bierlmeier, Jan ORCID: 0000-0002-7261-4744, Mund, Marcus, Lee, Jason E., Ries, Jonas ORCID: 0000-0002-6640-9250, Schwarzer, Dirk, Macek, Boris and Garcia-Saez, Ana J. (2022). DRP1 interacts directly with BAX to induce its activation and apoptosis. Embo J., 41 (8). HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jenner, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pena-Blanco, AidaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salvador-Gallego, RaquelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ugarte-Uribe, BegonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zollo, CristianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ganief, TariqUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bierlmeier, JanUNSPECIFIEDorcid.org/0000-0002-7261-4744UNSPECIFIED
Mund, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Jason E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ries, JonasUNSPECIFIEDorcid.org/0000-0002-6640-9250UNSPECIFIED
Schwarzer, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macek, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Saez, Ana J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-681596
DOI: 10.15252/embj.2021108587
Journal or Publication Title: Embo J.
Volume: 41
Number: 8
Date: 2022
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DYNAMIN-RELATED PROTEIN-1; MITOCHONDRIAL FISSION; CYTOCHROME-C; CELL-DEATH; MEMBRANE; DIMERIZATION; OLIGOMERIZATION; PLATFORM; REVEAL; POREMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68159

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