Abstract Mitochondria are key players of cellular metabolism, Ca2+ homeostasis, and apoptosis. The functionality of mitochondria is tightly regulated, and dysfunctional mitochondria are removed via mitophagy, a specialized form of autophagy that is compromised in hereditary forms of Parkinson’s disease. Through mitophagy, cells are able to cope with mitochondrial stress until the damage becomes too great, which leads to the activation of pro-apoptotic BCL-2 family proteins located on the outer mitochondrial membrane. Active pro-apoptotic BCL-2 proteins facilitate the release of cytochrome c from the mitochondrial intermembrane space (IMS) into the cytosol, committing the cell to apoptosis by activating a cascade of cysteinyl-aspartate specific proteases (caspases). We are only beginning to understand how the choice between mitophagy and the activation of caspases is determined on the mitochondrial surface. Intriguingly in neurons, caspase activation also plays a non-apoptotic role in synaptic plasticity. Here we review the current knowledge on the interplay between mitophagy and caspase activation with a special focus on the central nervous system.

中文翻译：

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杀死一个或杀死许多：线粒体自噬和细胞凋亡之间的相互作用

摘要 线粒体是细胞代谢、Ca2+ 稳态和细胞凋亡的关键参与者。线粒体的功能受到严格调控，功能失调的线粒体通过线粒体自噬去除，线粒体自噬是一种特殊形式的自噬，在遗传性帕金森病中受到损害。通过线粒体自噬，细胞能够应对线粒体压力，直到损伤变得太大，这导致位于线粒体外膜上的促凋亡 BCL-2 家族蛋白的激活。活性促凋亡 BCL-2 蛋白促进细胞色素 c 从线粒体膜间隙 (IMS) 释放到细胞质中，通过激活半胱氨酰-天冬氨酸特异性蛋白酶 (caspases) 级联使细胞发生凋亡。我们才刚刚开始了解线粒体表面如何决定线粒体自噬和半胱天冬酶激活之间的选择。有趣的是，在神经元中，半胱天冬酶激活也在突触可塑性中发挥非凋亡作用。在这里，我们回顾了当前关于线粒体自噬和半胱天冬酶激活之间相互作用的知识，特别关注中枢神经系统。