The membrane activity of BOK involves formation of large, stable toroidal pores and is promoted by cBID.

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)

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:

Fernandez Marrero, Yuniel; Bachmann, Daniel and Kaufmann, Thomas

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:

01 Apr 2018 02:30

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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