Gulbins Erich, Sassi Nicola, Grassmè Heike, Zoratti Mario, Szabò Ildikò
Department of Molecular Biology, University of Essen, Hufelandstrasse 5., Essen, Germany.
Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1251-9. doi: 10.1016/j.bbabio.2010.01.018. Epub 2010 Jan 28.
Mitochondria have been shown to play a pivotal role in apoptotic signalling in various cell types. We have recently reported that in lymphocytes the voltage-gated potassium channel Kv1.3, known to reside in the plasma membrane, is active also in the inner mitochondrial membrane. Upon induction of apoptosis, outer-membrane inserted Bax binds to and inhibits Kv1.3 resulting in hyperpolarization, an increase in reactive oxygen species production and cytochrome c release. In cells lacking Kv1.3 these events do not take place. Here, we present new data which further corroborates an important role of this channel in the sequence of events leading to Bax-induced cytochrome c release. Recombinant Kv1.3, when pre-incubated with Bax, prevents the actions of Bax at the level of mitochondria. Furthermore, we report the presence of Kv1.3 protein in mitochondria from PC3 and MCF-7 cancer cells, suggesting that this channel might play a role in the apoptotic signalling not only in lymphocytes but also in other cells.
线粒体已被证明在多种细胞类型的凋亡信号传导中起关键作用。我们最近报道，在淋巴细胞中，已知存在于质膜上的电压门控钾通道Kv1.3在内线粒体膜中也具有活性。诱导凋亡时，插入外膜的Bax与Kv1.3结合并抑制其活性，导致超极化、活性氧生成增加和细胞色素c释放。在缺乏Kv1.3的细胞中，这些事件不会发生。在此，我们提供了新的数据，进一步证实了该通道在导致Bax诱导细胞色素c释放的事件序列中的重要作用。重组Kv1.3与Bax预孵育时，可在 mitochondrial 水平上阻止Bax的作用。此外，我们报道了PC3和MCF-7癌细胞的线粒体中存在Kv1.3蛋白，表明该通道可能不仅在淋巴细胞中，而且在其他细胞的凋亡信号传导中发挥作用。
