Festjens Nele, van Gurp Marjan, van Loo Geert, Saelens Xavier, Vandenabeele Peter
Molecular Signaling and Cell Death Unit, Department of Molecular Biomedical Research, VIB and Ghent University, Ghent, Belgium.
Acta Haematol. 2004;111(1-2):7-27. doi: 10.1159/000074483.
In addition to their function as major energy-providing organelles of the cell, mitochondria accomplish a crucial role in apoptosis. The pro-apoptotic BH3-only members of the Bcl-2 family continuously sense the cellular integrity and well-being at various subcellular levels. If these sentinels are induced, released or activated, they converge on the release of mitochondrial intermembrane space proteins such as cytochrome c, the oxidoreductase AIF, endonuclease G, Smac/DIABLO and the serine protease Omi/HtrA2. We discuss how Bcl-2 family members integrate diverse survival and death signals and act as central regulators of apoptosis. Furthermore, we describe the current knowledge on the role of mitochondrial proteins in apoptotic cell death, discuss the molecular mechanisms of their release and the apoptotic role of mitochondria from a phylogenetic and immunological point of view.
除了作为细胞主要的能量供应细胞器发挥功能外，线粒体在细胞凋亡中也起着关键作用。Bcl-2家族中仅含BH3结构域的促凋亡成员持续在不同亚细胞水平感知细胞的完整性和健康状况。如果这些哨兵被诱导、释放或激活，它们会促使线粒体膜间隙蛋白如细胞色素c、氧化还原酶AIF、核酸内切酶G、Smac/DIABLO和丝氨酸蛋白酶Omi/HtrA2的释放。我们将讨论Bcl-2家族成员如何整合各种生存和死亡信号并作为细胞凋亡的核心调节因子发挥作用。此外，我们描述了目前关于线粒体蛋白在凋亡性细胞死亡中的作用的知识，从系统发育和免疫学角度讨论了它们释放的分子机制以及线粒体的凋亡作用。
