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首页> 外文期刊>Nature >DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C-elegans
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DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C-elegans

机译：ERP-1诱导的C-线虫细胞死亡期间DRP-1介导的线粒体片段化

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摘要

Genetic analyses in Caenorhabditis elegans have been instrumental in the elucidation of the central cell-death machinery, which is conserved from C. elegans to mammals(1,2). One possible difference that has emerged is the role of mitochondria. By releasing cytochrome c, mitochondria are involved in the activation of caspases in mammals(3,4). However, there has previously been no evidence that mitochondria are involved in caspase activation in C. elegans. Here we show that mitochondria fragment in cells that normally undergo programmed cell death during C. elegans development. Mitochondrial fragmentation is induced by the BH3-only protein EGL-1 and can be blocked by mutations in the bcl-2-like gene ced-9, indicating that members of the Bcl-2 family might function in the regulation of mitochondrial fragmentation in apoptotic cells. Mitochondrial fragmentation is independent of CED-4/Apaf-1 and CED-3/caspase, indicating that it occurs before or simultaneously with their activation. Furthermore, DRP-1/dynamin-related protein, a key component of the mitochondrial fission machinery, is required and sufficient to induce mitochondrial fragmentation and programmed cell death during C. elegans development. These results assign an important role to mitochondria in the cell-death pathway in C. elegans.
机译：秀丽隐杆线虫的遗传分析在阐明中央细胞死亡机制中起了重要作用，该机制从秀丽隐杆线虫到哺乳动物都是保守的（1,​​2）。已经出现的一种可能的差异是线粒体的作用。通过释放细胞色素c，线粒体参与了哺乳动物中胱天蛋白酶的活化（3,4）。但是，以前没有证据表明线粒体参与秀丽隐杆线虫中的胱天蛋白酶激活。在这里，我们显示线粒体片段在线虫发育过程中通常经历程序性细胞死亡的细胞中。线粒体片段化是由仅BH3蛋白EGL-1诱导的，并且可以被bcl-2-like基因ced-9中的突变所阻断，这表明Bcl-2家族的成员可能在凋亡的线粒体片段化调控中起作用。细胞。线粒体断裂独立于CED-4 / Apaf-1和CED-3 / caspase，表明它发生在激活之前或与其同时发生。此外，DRP-1 /动力蛋白相关蛋白（线粒体分裂机制的关键组成部分）是必需的，并且足以诱导线粒体发育过程中线粒体断裂和程序性细胞死亡。这些结果为线虫的细胞死亡途径中的线粒体发挥了重要作用。

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