Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
Volume 1797, Issue 6-7, Pages 1239-1244Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbabio.2010.01.021
Keywords
Channel; Outer membrane; Mitochondrion; Bcl-2; Pore; Self-assembly
Categories
Funding
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1023008] Funding Source: National Science Foundation
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A key, decision-making step in apoptosis is the release of proteins from the mitochondrial intermembrane space. Ceramide can self-assemble in the mitochondrial outer membrane to form large stable channels capable of releasing said proteins. Ceramide levels measured in mitochondria early in apoptosis are sufficient to form ceramide channels in the outer membrane. The channels are in dynamic equilibrium with non-conducting forms of ceramide in the membrane. This equilibrium can be strongly influenced by other sphingolipids and Bcl-2 family proteins. The properties of ceramide channels formed in a defined system, planar phospholipid membranes, demonstrate that proteins are not required for channel formation. In addition, experiments in the defined system reveal structural information. The results indicated that the channels are barrel-like structures whose staves are ceramide columns that span the membrane. Ceramide channels are good candidates for the protein release pathway that initiates the execution phase of apoptosis. (C) 2010 Elsevier B.V. All rights reserved.
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