Fernandez-Marrero, Yuniel; Bleicken, Stephanie; Das, Kushal Kumar; Bachmann, Daniel; Kaufmann, Thomas; Garcia-Saez, Ana J (2017). The membrane activity of BOK involves formation of large, stable toroidal pores and is promoted by cBID. FEBS journal, 284(5), pp. 711-724. Wiley-Blackwell 10.1111/febs.14008
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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-XL . 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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Fernández Marrero, Yuniel, Bachmann, Daniel, Kaufmann, Thomas (B) |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1742-464X |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Jana Berger |
Date Deposited: |
17 Aug 2017 13:11 |
Last Modified: |
29 Mar 2023 23:35 |
Publisher DOI: |
10.1111/febs.14008 |
PubMed ID: |
28064468 |
Uncontrolled Keywords: |
BOK ; apoptosis; liposome; mitochondria; pore |
BORIS DOI: |
10.7892/boris.96283 |
URI: |
https://boris.unibe.ch/id/eprint/96283 |
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