Journal article
Anti-apoptotic Bcl-2 Family Proteins Disassemble Ceramide Channels
The Journal of biological chemistry, v 283(11), pp 6622-6630
14 Mar 2008
PMID: 18171672
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Early in mitochondria-mediated apoptosis, the mitochondrial outer membrane becomes permeable to proteins that, when released into the cytosol, initiate the execution phase of apoptosis. Proteins in the Bcl-2 family regulate this permeabilization, but the molecular composition of the mitochondrial outer membrane pore is under debate. We reported previously that at physiologically relevant levels, ceramides form stable channels in mitochondrial outer membranes capable of passing the largest proteins known to exit mitochondria during apoptosis (Siskind, L. J., Kolesnick, R. N., and Colombini, M. (2006) Mitochondrion 6, 118-125). Here we show that Bcl-2 proteins are not required for ceramide to form protein-permeable channels in mitochondrial outer membranes. However, both recombinant human Bcl-x(L) and CED-9, the Caenorhabditis elegans Bcl-2 homologue, disassemble ceramide channels in the mitochondrial outer membranes of isolated mitochondria from rat liver and yeast. Importantly, Bcl-x L and CED-9 disassemble ceramide channels in the defined system of solvent-free planar phospholipid membranes. Thus, ceramide channel disassembly likely results from direct interaction with these anti-apoptotic proteins. Mutants of Bcl-x L act on ceramide channels as expected from their ability to be anti-apoptotic. Thus, ceramide channels may be one mechanism for releasing pro-apoptotic proteins from mitochondria during the induction phase of apoptosis.
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Details
- Title
- Anti-apoptotic Bcl-2 Family Proteins Disassemble Ceramide Channels
- Creators
- Leah J Siskind - Medical University of South CarolinaLaurence Feinstein - University of Maryland, College ParkTingxi Yu - Johns Hopkins MedicineJoseph S Davis - University of Maryland, College ParkDavid Jones - University of Maryland, College ParkJinna Choi - University of Maryland, College ParkJonathan E Zuckerman - Johns Hopkins UniversityWenzhi Tan - University of Maryland, College ParkR Blake Hill - Johns Hopkins UniversityJ Marie Hardwick - Johns Hopkins MedicineMarco Colombini - University of Maryland, College Park
- Publication Details
- The Journal of biological chemistry, v 283(11), pp 6622-6630
- Publisher
- ASBMB Publications / Elsevier
- Grant note
- GM067180 / NIGMS NIH HHS R01 GM077875-03 / NIGMS NIH HHS R01 NS037402 / NINDS NIH HHS NS42025 / NINDS NIH HHS R01 NS042025 / NINDS NIH HHS R01 GM077875 / NIGMS NIH HHS GM77875 / NIGMS NIH HHS NS37402 / NINDS NIH HHS R01 GM067180-04 / NIGMS NIH HHS R01 GM067180 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000253779600003
- Scopus ID
- 2-s2.0-43749120533
- Other Identifier
- 991021838155604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology