The membrane activity of BOK involves formation of large, stable toroidal pores and is promoted by cBID
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The BCL‐2 family members are key regulators of the intrinsic apoptotic pathway, which is defined by permeabilization of the mitochondrial outer membrane by members of the BAX‐like subfamily. BOK is classified as a BAX‐like protein; however, its (patho‐)physiological role remains largely unclear. We therefore assessed the membrane permeabilization potential of C‐terminally truncated recombinant BOK, BOK∆C. We show that BOK∆C can permeabilize liposomes mimicking the composition of mitochondrial outer membrane, but not of endoplasmic reticulum, forming large and stable pores over time. Importantly, pore formation was enhanced by the presence of cBID and refractory to the addition of antiapoptotic BCL‐X L. However, isolated mitochondria from Bax−/−Bak−/− cells were resistant to BOK‐induced cytochrome c release, even in the presence of cBID. Taken together, we show that BOK∆C can permeabilize liposomes, and cooperate with cBID, but its role in directly mediating mitochondrial permeabilization is unclear and may underlie a yet to be determined negative regulation.
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BOK has been shown to induce MOMP in the absence of BAX and BAK and independently of other BCL2 family members.
“Moreover, BOK has recently been shown to induce MOMP in the absence of BAX and BAK and independently of other BCL2 family members [47, 151, 152].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [151]
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- Authors
- Fernández‐Marrero, Y., Bleicken, S., Das, K. K., Bachmann, D., Kaufmann, T., & Garcia‐Saez, A. J.
- Affiliations
- University of Bern (CH)
- University of Tübingen (DE)
- Interfaculty Institute of Biochemistry University of Tübingen Germany
- Corresponding author
- Kaufmann, Thomas
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2017-02
- Volume
- 284
- Issue
- 5
- Pages
- 711-724
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W2568609865
- Cited by
- 47
- References
- 50
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 6
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, other-oa)
- Open Access CRIS of the University of Bern
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030E150805)
- Deutsche Forschungsgemeinschaft (GA1641/2‐1, EXC 1069)
- European Research Council (ERC‐2012‐StG‐309966)
- 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
- BOK, Bcl-2 family proteins, mitochondrial outer membrane permeabilization, toroidal pores, Bcl-xL, cytochrome c release, mitochondrial apoptosis, liposome permeabilization
- MeSH terms
- Animals, Cell Membrane Permeability, Endoplasmic Reticulum, Liposomes, Recombinant Proteins, Signal Transduction, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Cytochromes c, bcl-X Protein, Mitochondrial Membranes, Mice, Gene Knockout Techniques
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