Department of Pathology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
Biochem Biophys Res Commun. 2012 Apr 27;421(1):81-5. doi: 10.1016/j.bbrc.2012.03.118. Epub 2012 Apr 2.
Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116 and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.
线粒体在调控细胞凋亡（一种程序性细胞死亡形式）中起着关键作用，通过释放细胞色素 c 等促凋亡因子。越来越多的证据表明，线粒体形态的动态变化参与了细胞凋亡反应。然而，DRP1 介导的线粒体裂变是否需要诱导细胞凋亡仍存在推测。在这里，我们表明，siRNA 介导的 DRP1 敲低促进了 HCT116 和 SW480 人结肠癌细胞中伸长线粒体的积累。令人惊讶的是，DRP1 的下调导致这些细胞的增殖减少和凋亡增加。在 DRP1 耗尽的细胞中还发现了更高的细胞色素 c 释放率和线粒体膜电位降低。总之，我们目前的研究结果表明，线粒体裂变因子 DRP1 通过调节细胞色素 c 释放和线粒体膜完整性来抑制结肠癌细胞凋亡。
