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Bax assembly into rings and arcs in apoptotic mitochondria is linked to membrane pores
Open accessAbstract
Bax is a key regulator of apoptosis that, under cell stress, accumulates at mitochondria, where it oligomerizes to mediate the permeabilization of the mitochondrial outer membrane leading to cytochrome c release and cell death. However, the underlying mechanism behind Bax function remains poorly understood. Here, we studied the spatial organization of Bax in apoptotic cells using dual-color single-molecule localization-based super-resolution microscopy. We show that active Bax clustered into a broad distribution of distinct architectures, including full rings, as well as linear and arc-shaped oligomeric assemblies that localized in discrete foci along mitochondria. Remarkably, both rings and arcs assemblies of Bax perforated the membrane, as revealed by atomic force microscopy in lipid bilayers. Our data identify the supramolecular organization of Bax during apoptosis and support a molecular mechanism in which Bax fully or partially delineates pores of different sizes to permeabilize the mitochondrial outer membrane.
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“Oligomerization ultimately leads to the assembly of a toroidal lipidic pore that alters mitochondrial permeability and causes profound rearrangements of the mitochondrial ultrastructure [78, 84–86].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [84]
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Metadata
- Authors
- Salvador‐Gallego, R., Mund, M., Cosentino, K., Schneider, J., Unsay, J., Schraermeyer, U., Engelhardt, J., Ries, J., & García‐Sáez, A. J.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Max Planck Institute for Intelligent Systems (DE)
- German Cancer Research Center (DE)
- Universitätsklinikum Tübingen (DE)
- Corresponding author
- Ries, Jonas
- García‐Sáez, Ana J
- ORCID
- Venue
- The EMBO Journal
- Published
- 2016-01-18
- Volume
- 35
- Issue
- 4
- Pages
- 389-401
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4755116
- OpenAlex
- W2259902722
- Cited by
- 296
- References
- 50
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 23 · 2023: 26 · 2022: 26 · 2021: 30 · 2020: 38 · 2019: 28 · 2018: 24 · 2017: 40 · 2016: 26
- FWCI
- 20.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion)
- Funders
- European Research Council (ERC‐2012‐StG 309966)
- Max Planck Society
- German Cancer Research Center
- Deutsche Forschungsgemeinschaft (FOR 2036)
- European Molecular Biology Laboratory
- EMBL International PhD Programme
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- Bax, apoptosis, mitochondrial outer membrane permeabilization, Bax oligomerization, membrane pores, cytochrome c release, supramolecular organization
- MeSH terms
- HeLa Cells, Humans, Microscopy, Fluorescence, Mitochondria, Permeability, Apoptosis, Cytochromes c, Microscopy, Electron, Transmission, bcl-2-Associated X Protein, Mitochondrial Membranes, Pore Forming Cytotoxic Proteins, Protein Multimerization
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