Cho Hyo Min, Sun Woong
Department of Anatomy, Korea University College of Medicine, Brain Korea 21, Seoul 02841, Korea.
Exp Neurobiol. 2015 Sep;24(3):219-25. doi: 10.5607/en.2015.24.3.219. Epub 2015 Sep 17.
Cells undergo apoptosis mainly via two pathways-the mitochondrial pathway and the cytosolic pathway. It has been well documented that activation of the mitochondrial pathway promotes mitochondrial fragmentation and inhibition of mitochondrial fragmentation partly represses cell death. However, the mitochondrial events following activation of the cytosolic pathway are less understood. In this study, we treated Fas-activating antibody and found mitochondrial fragmentation without cell death in hippocampal primary neurons and HT-22 cell lines. Fas antibody treatment, in fact, promoted rapid activation of caspase-8, while executioner caspase-3 activation was not observed. Furthermore, blockage of caspase-8 efficiently prevented Fas antibody-induced mitochondrial fragmentation. These results suggest that the cytosolic pathway induced by death receptor activation promotes caspase-8-dependent mitochondrial fission.
细胞主要通过两条途径发生凋亡——线粒体途径和胞质途径。已有充分证据表明，线粒体途径的激活会促进线粒体碎片化，而抑制线粒体碎片化则部分抑制细胞死亡。然而，胞质途径激活后的线粒体事件尚不太清楚。在本研究中，我们用Fas激活抗体处理，发现在海马原代神经元和HT-22细胞系中，线粒体发生碎片化但无细胞死亡。事实上，Fas抗体处理促进了caspase-8的快速激活，而未观察到执行性caspase-3的激活。此外，caspase-8的阻断有效阻止了Fas抗体诱导的线粒体碎片化。这些结果表明，死亡受体激活诱导的胞质途径促进了caspase-8依赖性的线粒体分裂。
