Beatson Institute, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, United Kingdom.
Cold Spring Harb Perspect Biol. 2013 Sep 1;5(9):a008706. doi: 10.1101/cshperspect.a008706.
Although required for life, paradoxically, mitochondria are often essential for initiating apoptotic cell death. Mitochondria regulate caspase activation and cell death through an event termed mitochondrial outer membrane permeabilization (MOMP); this leads to the release of various mitochondrial intermembrane space proteins that activate caspases, resulting in apoptosis. MOMP is often considered a point of no return because it typically leads to cell death, even in the absence of caspase activity. Because of this pivotal role in deciding cell fate, deregulation of MOMP impacts on many diseases and represents a fruitful site for therapeutic intervention. Here we discuss the mechanisms underlying mitochondrial permeabilization and how this key event leads to cell death through caspase-dependent and -independent means. We then proceed to explore how the release of mitochondrial proteins may be regulated following MOMP. Finally, we discuss mechanisms that enable cells sometimes to survive MOMP, allowing them, in essence, to return from the point of no return.
尽管线粒体对于生命是必需的，但矛盾的是，它们常常是启动细胞凋亡的关键。线粒体通过一种称为线粒体外膜通透性（MOMP）的事件来调节半胱天冬酶的激活和细胞死亡；这导致各种线粒体膜间隙蛋白的释放，这些蛋白激活半胱天冬酶，导致细胞凋亡。MOMP 通常被认为是一个不归点，因为它通常会导致细胞死亡，即使没有半胱天冬酶的活性。由于在决定细胞命运方面的关键作用，MOMP 的失调会影响许多疾病，并代表着治疗干预的一个有成效的靶点。在这里，我们讨论了线粒体通透性的机制，以及这一关键事件如何通过依赖和不依赖半胱天冬酶的方式导致细胞死亡。然后，我们继续探讨线粒体蛋白释放如何在 MOMP 后被调节。最后，我们讨论了使细胞有时能够在 MOMP 后存活的机制，使它们在本质上能够从不归点返回。
