Colombini Marco
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1239-44. doi: 10.1016/j.bbabio.2010.01.021. Epub 2010 Jan 25.
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.
细胞凋亡过程中一个关键的决策步骤是线粒体外膜间隙的蛋白质释放。神经酰胺能够在线粒体外膜中自组装形成大型稳定通道，从而释放上述蛋白质。在细胞凋亡早期，线粒体内测得的神经酰胺水平足以在外膜中形成神经酰胺通道。这些通道与膜中不导电形式的神经酰胺处于动态平衡。这种平衡会受到其他鞘脂和Bcl-2家族蛋白的强烈影响。在特定系统——平面磷脂膜中形成的神经酰胺通道的特性表明，通道形成不需要蛋白质。此外，在该特定系统中进行的实验揭示了结构信息。结果表明，这些通道是桶状结构，其桶板是跨越膜的神经酰胺柱。神经酰胺通道很可能是启动细胞凋亡执行阶段的蛋白质释放途径。
