Cited by 296Cell death mechanisms and regulationMitochondrial Function and PathologyAutophagy in Disease and Therapy

Bax assembly into rings and arcs in apoptotic mitochondria is linked to membrane pores

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Salvador‐Gallego, Raquel, Mund, Markus, Cosentino, Katia, Schneider, Jale, Unsay, Joseph, Schraermeyer, Ulrich, Engelhardt, Johann, Ries, Jonas +1 more·2016·The EMBO Journal

Abstract

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 of BAX and BAK ultimately leads to the assembly of a toroidal lipidic pore that alters mitochondrial permeability and causes profound rearrangements of the mitochondrial ultrastructure.

    “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].”

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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
Venue
The EMBO Journal
Published
2016-01-18
Volume
35
Issue
4
Pages
389-401
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
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
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
  • Health Sciences › Medicine › Epidemiology › 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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