Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling

Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling
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小脑颗粒神经元凋亡中细胞色素 C 释放先于线粒体膜电位损失:线粒体肿胀缺失

DOI:
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发表时间:
2002
影响因子:
4.7
通讯作者:
M. Haak‐Frendscho
M. Haak‐Frendscho
中科院分区:
医学2区
文献类型:
--
作者:
Susan S. Wigdal;R. Kirkland;J. Franklin;M. Haak‐Frendscho

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已经表明,细胞凋亡死亡期间细胞色素c(Cyt c)从线粒体的释放是通过线粒体渗透性转换孔的打开,随后是线粒体外膜的肿胀诱导的破裂。然而,这仍然是有争议的,可能会因细胞类型和模型系统而异。我们确定,在小鼠小脑颗粒神经元中,细胞色素c的重新分布先于凋亡过程中线粒体膜电位的丧失,这表明孔在释放之前没有打开。电镜观察线粒体形态学变化,发现Cyt c释放过程中线粒体无明显肿胀。这表明孔的作用机制,如果有的话,不是通过线粒体外膜破裂。虽然邦克酸,孔开放的抑制剂,适度延迟凋亡死亡,但它也引起蛋白质合成的显著抑制(p<0.05)。 放线菌酮对蛋白质合成的等效抑制具有类似的延迟效应,表明米松酸的作用是非特异性的。这些结果表明,线粒体渗透性转换孔不参与细胞色素c从线粒体的小脑颗粒神经元的凋亡死亡过程中释放。
It has been suggested that release of cytochrome c (Cyt c) from mitochondria during apoptotic death is through opening of the mitochondrial permeability transition pore followed by swelling‐induced rupture of the mitochondrial outer membrane. However, this remains controversial and may vary with cell type and model system. We determined that in mouse cerebellar granule neurons, Cyt c redistribution preceded the loss of mitochondrial membrane potential during the apoptotic process, suggesting that the pore did not open prior to release. Furthermore, when mitochondria were morphologically assessed by electron microscopy, they were not obviously swollen during the period of Cyt c release. This indicates that the pore mechanism of action, if any, is not through mitochondrial outer membrane rupture. While bongkrekic acid, an inhibitor of pore opening, modestly delayed apoptotic death, it also caused a significant (p < 0.05) suppression of protein synthesis. An equivalent suppression of protein synthesis by cycloheximide had a similar delaying effect, suggesting that bongkrekic acid was acting non‐specifically. These findings suggest that mitochondrial permeability transition pore is not involved in Cyt c release from mitochondria during the apoptotic death of cerebellar granule neurons.
DOI: 10.1021/bi00232a015
发表时间: 1991-05-07
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
REERS, M;SMITH, TW;CHEN, LB
通讯作者: CHEN, LB
DOI: 10.1152/ajpcell.1997.273.2.c479
发表时间: 1997-08-01
影响因子: 5.5
作者:
Simbula, G;Glascott, PA;Farber, JL
通讯作者: Farber, JL