The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis
The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis
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DOI：
10.1038/sj.cdd.4401552
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发表时间：
2005-03-01
影响因子：
12.4
通讯作者：
Heidenreich, KA
中科院分区：
文献类型：
--
作者：
Precht, TA;Phelps, RA;Heidenreich, KA
小脑颗粒神经元（CGN）需要去极化以在培养物中存活。当被剥夺这种刺激时，CGN通过涉及Bim诱导、Bax易位、细胞色素c释放和半胱天冬酶-9和-3活化的内在凋亡级联而死亡。线粒体通透性转换孔（mPTP）的开放是内源性细胞凋亡的早期事件，然而，mPTP开放在神经元凋亡中的确切作用目前尚不清楚。在这里，我们表明，mPTP开放作为一个启动事件，刺激Bax易位到线粒体。组成性定位于线粒体的C-末端（α 9螺旋）GFP-Bax点突变体（T182 A）规避了mPTP开放的要求，并且完全足以诱导CGN凋亡。总的来说，这些数据表明，在CGN细胞凋亡中mPTP开放的主要作用是触发Bax易位到线粒体，最终导致细胞色素c释放和半胱天冬酶激活。
Cerebellar granule neurons (CGNs) require depolarization for their survival in culture. When deprived of this stimulus, CGNs die via an intrinsic apoptotic cascade involving Bim induction, Bax translocation, cytochrome c release, and caspase-9 and -3 activation. Opening of the mitochondrial permeability transition pore (mPTP) is an early event during intrinsic apoptosis; however, the precise role of mPTP opening in neuronal apoptosis is presently unclear. Here, we show that mPTP opening acts as an initiating event to stimulate Bax translocation to mitochondria. A C-terminal (alpha9 helix) GFP-Bax point mutant (T182A) that constitutively localizes to mitochondria circumvents the requirement for mPTP opening and is entirely sufficient to induce CGN apoptosis. Collectively, these data indicate that the major role of mPTP opening in CGN apoptosis is to trigger Bax translocation to mitochondria, ultimately leading to cytochrome c release and caspase activation.