Consequences of the combined loss of BOK and BAK or BOK and BAX
Open accessAbstract
The multi-BCL-2 homology domain pro-apoptotic BCL-2 family members BAK and BAX have critical roles in apoptosis. They are essential for mitochondrial outer-membrane permeabilization, leading to the release of apoptogenic factors such as cytochrome-c, which promote activation of the caspase cascade and cellular demolition. The BOK protein has extensive amino-acid sequence similarity to BAK and BAX and is expressed in diverse cell types, particularly those of the female reproductive tissues. The BOK-deficient mice have no readily discernible abnormalities, and its function therefore remains unresolved. We hypothesized that BOK may exert functions that overlap with those of BAK and/or BAX and examined this by generating Bok(-/-)Bak(-/-) and Bok(-/-)Bax(-/-) mice. Combined loss of BOK and BAK did not elicit any noticeable defects, although it remains possible that BOK and BAK have critical roles in developmental cell death that overlap with those of BAX. In most tissues examined, loss of BOK did not exacerbate the abnormalities caused by loss of BAX, such as defects in spermatogenesis or the increase in neuronal populations in the brain and retina. Notably, however, old Bok(-/-)Bax(-/-) females had abnormally increased numbers of oocytes from different stages of development, indicating that BOK may have a pro-apoptotic function overlapping with that of BAX in age-related follicular atresia.
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Bok−/−, Bax−/−Bok−/− as well as Bak1−/−Bok−/− mice display no obvious abnormalities (except for persistence of primordial follicle oocytes in aged Bax−/−Bok−/− females).
“Of note, Bok−/−, Bax−/−Bok−/− as well as Bak1−/−Bok−/− mice display no obvious abnormalities (except for persistence of primordial follicle oocytes in aged Bax−/−Bok−/− females) [154, 155]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [155]
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Self-citation
- Authors
- Ke, F., Bouillet, P., Kaufmann, T., Strasser, A., Kerr, J., & Voss, A. K.
- Affiliations
- Walter and Eliza Hall Institute of Medical Research (AU)
- The University of Melbourne (AU)
- University of Bern (CH)
- Monash University (AU)
- Corresponding author
- Strasser, A
- Venue
- Cell Death & Disease
- Published
- 2013-06-06
- Volume
- 4
- Issue
- 6
- Pages
- e650-e650
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3698543
- OpenAlex
- W2077829449
- Cited by
- 72
- References
- 29
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 9 · 2020: 8 · 2019: 2 · 2018: 4 · 2017: 9 · 2016: 12 · 2015: 6 · 2014: 6 · 2013: 3
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Open Access CRIS of the University of Bern
- Funders
- National Science Foundation (1016701)
- Leukemia Research Foundation
- Australian Government
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (119203)
- Stanford Institute for Research in the Social Sciences
- Medical Research Council (1016701, 461221)
- National Health and Medical Research Council (461221, 1016701, 575512, 1042629, 1020363)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- BOK, Bak, Bax, Bcl-2 family proteins, apoptosis, mitochondrial outer membrane permeabilization, cytochrome c release, caspase activation, oocyte apoptosis, follicular atresia, spermatogenesis, neuronal proliferation, female reproductive tissues, developmental cell death
- MeSH terms
- Animals, Brain, Cell Survival, Cells, Cultured, Female, Ovarian Follicle, Lymphocytes, Male, Mice, Inbred C57BL, Retina, Spleen, Testis, Apoptosis, Mice, Knockout, Proto-Oncogene Proteins c-bcl-2, Myeloid Cells, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Mice, Mice, 129 Strain
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