hFis1, a novel component of the mammalian mitochondrial fission machinery

hFis1, a novel component of the mammalian mitochondrial fission machinery
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DOI:
10.1074/jbc.m303758200
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发表时间:
2003-09-19
影响因子:
4.8
通讯作者:
Martinou, JC
Martinou, JC
中科院分区:
生物学2区
文献类型:
--
作者:
James, DI;Parone, PA;Martinou, JC

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分裂和融合机制之间的平衡调节线粒体的形态。在这项研究中,我们已经确定了一种哺乳动物蛋白质,我们称之为hFis 1,这是已知参与酵母线粒体分裂的酵母Fis 1 p的直系同源物。hFis 1,当在各种细胞类型中过表达时,定位于线粒体外膜并诱导线粒体分裂。这一事件被抑制的显性负突变体Drp 1(Drp 1(K38 A)),裂变装置的主要组成部分。由hFis 1的线粒体网络的片段化之后,细胞色素c的释放,并最终凋亡。Bcl-x(L)能够阻断细胞色素c释放和细胞凋亡,但不能阻止线粒体断裂。我们的研究表明,hFis 1是哺乳动物的裂变机制的一部分,并建议,裂变过程的调节可能参与凋亡机制。
The balance between the fission and fusion mechanisms regulate the morphology of mitochondria. In this study we have identified a mammalian protein that we call hFis1, which is the orthologue of the yeast Fis1p known to participate in yeast mitochondrial division. hFis1, when overexpressed in various cell types, localized to the outer mitochondrial membrane and induced mitochondrial fission. This event was inhibited by a dominant negative mutant of Drp1 ( Drp1( K38A)), a major component of the fission apparatus. Fragmentation of the mitochondrial network by hFis1 was followed by the release of cytochrome c and ultimately apoptosis. Bcl-x(L) was able to block cytochrome c release and apoptosis but failed to prevent mitochondrial fragmentation. Our studies show that hFis1 is part of the mammalian fission machinery and suggest that regulation of the fission processes might be involved in apoptotic mechanisms.