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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >OPA1 requires mitofusin 1 to promote mitochondrial fusion.
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OPA1 requires mitofusin 1 to promote mitochondrial fusion.

机译:OPA1需要线粒体蛋白1来促进线粒体融合。

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摘要

The regulated equilibrium between mitochondrial fusion and fission is essential to maintain integrity of the organelle. Mechanisms of mitochondrial fusion are largely uncharacterized in mammalian cells. It is unclear whether OPA1, a dynamin-related protein of the inner membrane mutated in autosomal dominant optic atrophy, participates in fusion or fission. OPA1 promoted the formation of a branched network of elongated mitochondria, requiring the integrity of both its GTPase and C-terminal coiled-coil domain. Stable reduction of OPA1 levels by RNA interference resulted in small, fragmented, and scattered mitochondria. Levels of OPA1 did not affect mitochondrial docking, but they correlated with the extent of fusion as measured by polyethylene glycol mitochondrial fusion assays. A genetic analysis proved that OPA1 was unable to tubulate and fuse mitochondria lacking the outer membrane mitofusin 1 but not mitofusin 2. Our data show that OPA1 functionally requires mitofusin 1 to regulate mitochondrial fusion and reveal a specific functional difference between mitofusin 1 and 2.
机译:线粒体融合与裂变之间的调节平衡对于维持细胞器的完整性至关重要。线粒体融合的机制在哺乳动物细胞中主要是未知的。尚不清楚OPA1是常染色体显性视神经萎缩突变的内膜的一种与动力蛋白有关的蛋白,是否参与融合或裂变。 OPA1促进了延长的线粒体分支网络的形成,要求其GTPase和C末端卷曲螺旋结构域的完整性。 RNA干扰可稳定降低OPA1水平,从而导致线粒体较小,碎片化和分散。 OPA1的水平不影响线粒体对接,但与聚乙二醇线粒体融合测定法测定的融合程度相关。遗传分析证明,OPA1不能输卵管和融合缺乏外膜丝裂霉素1而没有丝裂霉素2的线粒体。我们的数据显示,OPA1功能上需要丝裂霉素1来调节线粒体融合,并揭示了丝裂霉素1和2之间的特定功能差异。

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