Bax assembles into large ring‐like structures remodeling the mitochondrial outer membrane in apoptosis
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The Bcl‐2 family proteins Bax and Bak are essential for the execution of many apoptotic programs. During apoptosis, Bax translocates to the mitochondria and mediates the permeabilization of the outer membrane, thereby facilitating the release of pro‐apoptotic proteins. Yet the mechanistic details of the Bax‐induced membrane permeabilization have so far remained elusive. Here, we demonstrate that activated Bax molecules, besides forming large and compact clusters, also assemble, potentially with other proteins including Bak, into ring‐like structures in the mitochondrial outer membrane. STED nanoscopy indicates that the area enclosed by a Bax ring is devoid of mitochondrial outer membrane proteins such as Tom20, Tom22, and Sam50. This strongly supports the view that the Bax rings surround an opening required for mitochondrial outer membrane permeabilization (MOMP). Even though these Bax assemblies may be necessary for MOMP, we demonstrate that at least in Drp1 knockdown cells, these assemblies are not sufficient for full cytochrome c release. Together, our super‐resolution data provide direct evidence in support of large Bax‐delineated pores in the mitochondrial outer membrane as being crucial for Bax‐mediated MOMP in cells.
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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].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [85]
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- Authors
- Große, L., Wurm, C. A., Brüser, C., Neumann, D., Jans, D. C., & Jakobs, S.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- Corresponding author
- Jans, Daniel C
- Jakobs, Stefan
- Venue
- The EMBO Journal
- Published
- 2016-01-18
- Volume
- 35
- Issue
- 4
- Pages
- 402-413
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4755111
- OpenAlex
- W2273341597
- Cited by
- 281
- References
- 56
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 14 · 2023: 27 · 2022: 19 · 2021: 26 · 2020: 33 · 2019: 40 · 2018: 30 · 2017: 36 · 2016: 28
- FWCI
- 23.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- GRO (submittedVersion, cc-by)
- Funders
- Cluster of Excellence and DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain
- 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, mitochondrial outer membrane permeabilization, apoptosis, Bcl-2 family proteins, Bak, cytochrome c release, Drp1, Tom20, Tom22, Sam50, protein clustering, STED microscopy
- MeSH terms
- Cell Line, Humans, Microscopy, Fluorescence, Mitochondria, Permeability, Apoptosis, Cytochromes c, bcl-2-Associated X Protein, Mitochondrial Membranes, Pore Forming Cytotoxic Proteins, Protein Multimerization
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