Sphingolipids: Basic Science and Drug Development by Erich Gulbins & Irina Petrache

Author:Erich Gulbins & Irina Petrache
Language: eng
Format: epub
Publisher: Springer Vienna, Vienna

10 Conclusion

The permeabilization of the MOM to proteins results in the release of intermembrane-space proteins leading to the onset of the execution phase of apoptosis. This permeabilization, generally attributed to the action of the pro-apoptotic proteins, Bax and BAK, may be far more complex. Liposome and planar membrane experiments clearly show that Bax does not need ceramide to form channels and vice versa. However, the reported synergy between these agents indicates evolutionary selection for this interaction. Also the regulation of ceramide channels by anti-apoptotic proteins reinforces the conclusion that ceramide and Bcl-2 family proteins are both involved in MOM permeabilization. The unique ability of ceramide to form large stable channels capable of translocating proteins through membranes can hardly be an accidental occurrence but rather an evolutionarily conserved process. The structure of ceramide is not merely an accident but selected for based on its functional characteristics: one of these being the ability to form channels.

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