Mdm30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast

Mdm30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast
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DOI:
10.1091/mbc.e02-12-0831
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发表时间:
2003-06-01
影响因子:
3.3
通讯作者:
Westermann, B
Westermann, B
中科院分区:
生物学3区
文献类型:
--
作者:
Fritz, S;Weinbach, N;Westermann, B

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线粒体融合和裂变对线粒体形态和功能起着重要作用。我们确定 Mdm30 是维持酵母中具有融合能力的线粒体所需的新成分。 Mdm30 序列包含一个 F-box 基序,该基序常见于 Skp1-Cdc53-F-box 蛋白泛素连接酶的亚基中。 Mdm30 的一部分与线粒体相关。缺乏 Mdm30 的细胞含有高度聚集或碎片化的线粒体,而不是野生型细胞中看到的分支管状网络。 Deltamdm30 细胞在高温下会丢失线粒体 DNA,并且无法融合线粒体。在所有温度下的受精卵中。这些缺陷可以通过删除 DNM1 来弥补,DNM1 是编码线粒体分裂机制的一个组成部分的基因。 Fzo1 是线粒体融合机制的关键组成部分,其蛋白质水平受 Mdm30 调节。缺乏 Mdm30 的细胞或从异源启动子过度表达 Fzo1 的细胞中,Fzo1 水平升高会以类似的方式诱导线粒体聚集。我们的结果表明,Mdm30 通过调节 Fzo1 的稳态水平来控制线粒体形状,并指出泛素/26S 蛋白酶体系统和线粒体之间的联系。
Mitochondrial fusion and fission play important roles for mitochondrial morphology and function. We identified Mdm30 as a novel component required for maintenance of fusion-competent mitochondria in yeast. The Mdm30 sequence contains an F-box motif that is commonly found in subunits of Skp1-Cdc53-F-box protein ubiquitin ligases. A fraction of Mdm30 is associated with mitochondria. Cells lacking Mdm30 contain highly aggregated or fragmented mitochondria instead of the branched tubular network seen in wild-type cells. Deltamdm30 cells lose mitochondrial DNA at elevated temperature and fail to fuse mitochondria. in zygotes at all temperatures. These defects are rescued by deletion of DNM1, a gene encoding a component of the mitochondrial division machinery. The protein level of Fzo1, a key component of the mitochondrial fusion machinery, is regulated by Mdm30. Elevated Fzo1 levels in cells lacking Mdm30 or in cells overexpressing Fzo1 from a heterologous promoter induce mitochondrial aggregation in a similar manner. Our results suggest that Mdm30 controls mitochondrial shape by regulating the steady-state level of Fzo1 and point to a connection of the ubiquitin/26S proteasome system and mitochondria.