OPA1 alternate splicing uncouples an evolutionary conserved function in mitochondrial fusion from a vertebrate restricted function in apoptosis
OPA1 alternate splicing uncouples an evolutionary conserved function in mitochondrial fusion from a vertebrate restricted function in apoptosis
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DOI：
10.1038/sj.cdd.4402048
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发表时间：
2007-04-01
影响因子：
12.4
通讯作者：
Lenaers, G.
中科院分区：
文献类型：
--
作者：
Olichon, A.;ElAchouri, G.;Lenaers, G.
在大多数真核细胞中，凋亡蛋白从线粒体的释放涉及线粒体网络的分裂和嵴结构的急剧重塑。线粒体内动力蛋白OPA1，作为这些过程的一个潜在的中央演员，存在作为八个异构体产生的外显子（Ex）4，4b和5b的选择性剪接组合，其功能仍然不确定。在这里，我们表明，Ex4是保守的，在整个进化过程中赋予OPA1的功能，参与维护的Delta Psi m和线粒体网络的融合。相反，Ex4b和Ex5b是脊椎动物特异性的，定义了参与细胞色素c释放的功能，细胞凋亡过程也限于脊椎动物。不同器官中OPA1变异体丰度的剧烈变化表明，核剪接可以控制线粒体的动态命运和对凋亡和病理的易感性。
In most eucaryote cells, release of apoptotic proteins from mitochondria involves fission of the mitochondrial network and drastic remodelling of the cristae structures. The intramitochondrial dynamin OPA1, as a potential central actor of these processes, exists as eight isoforms resulting from the alternate splicing combinations of exons ( Ex) 4, 4b and 5b, which functions remain undetermined. Here, we show that Ex4 that is conserved throughout evolution confers functions to OPA1 involved in the maintenance of the Delta Psi m and in the fusion of the mitochondrial network. Conversely, Ex4b and Ex5b, which are vertebrate specific, define a function involved in cytochrome c release, an apoptotic process also restricted to vertebrates. The drastic changes of OPA1 variant abundance in different organs suggest that nuclear splicing can control mitochondrial dynamic fate and susceptibility to apoptosis and pathologies.