The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis
The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis
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DOI：
10.1016/s1534-5807(01)00055-7
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发表时间：
2001-10-01
影响因子：
11.8
通讯作者：
Youle, RJ
中科院分区：
文献类型：
--
作者：
Frank, S;Gaume, B;Youle, RJ
在健康细胞中，融合和分裂事件参与调节线粒体的形态。在细胞凋亡过程中，线粒体网分裂成多个点状细胞器，这使得我们研究了DRp1的作用，这是一种与动力蛋白相关的蛋白，介导线粒体膜的外膜分裂。在诱导细胞凋亡时，Drp1从胞浆移位到线粒体，在线粒体中它优先定位于细胞器分裂的潜在位置。通过显性-负性突变体的过表达抑制Drp1可以抵消向点状线粒体表型的转化，防止线粒体膜电位的丧失和细胞色素c的释放，并显示细胞器的可复制肿胀。值得注意的是，抑制Drp1可以阻止细胞死亡，暗示线粒体分裂是细胞凋亡的重要步骤。
In healthy cells, fusion and fission events participate in regulating mitochondrial morphology. Disintegration of the mitochondrial reticulum into multiple punctiform organelles during apoptosis led us to examine the role of Drp1, a dynamin-related protein that mediates outer mitochondrial membrane fission. Upon induction of apoptosis, Drp1 translocates from the cytosol to mitochondria, where it preferentially localizes to potential sites of organelle division. Inhibition of Drp1 by overexpression of a dominant-negative mutant counteracts the conversion to a punctiform mitochondrial phenotype, prevents the loss of the mitochondrial membrane potential and the release of cytochrome c, and reveals a reproducible swelling of the organelles. Remarkably, inhibition of Drp1 blocks cell death, implicating mitochondrial fission as an important step in apoptosis.