clueless, a conserved Drosophila gene required for mitochondrial subcellular localization, interacts genetically with parkin
clueless, a conserved Drosophila gene required for mitochondrial subcellular localization, interacts genetically with parkin
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DOI：
10.1242/dmm.002378
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发表时间：
2009-09-01
影响因子：
4.3
通讯作者：
Spradling, Allan C.
中科院分区：
文献类型：
--
作者：
Cox, Rachel T.;Spradling, Allan C.
帕金森病与线粒体功能改变有关。Parkin（park）是果蝇中一种人类基因的直系同源物，与许多帕金森氏病家族病例有关，其突变缩短了寿命，消除了生育能力并破坏了线粒体结构。然而，Park在线粒体功能中所起的作用仍不清楚。在这里，我们描述了一种新的果蝇基因，clueless（CLU），它编码一个高度保守的tetratricopeptide重复蛋白，是密切相关的CluA蛋白的Dictyosteelium，Clu1的酿酒酵母和类似的蛋白质在不同的后生动物真核生物从拟南芥到人类。像它的直系同源物一样，果蝇clu的缺失导致线粒体在细胞内聚集。我们发现，强clu突变类似于公园突变的线粒体功能的影响，这两个基因在遗传上相互作用。相反，park纯合子中的线粒体变得高度聚集。我们提出，Clu的功能在一个新的途径，根据其生理状态的细胞内的线粒体的位置。Clu通路的破坏可能会增强氧化损伤，改变基因表达，导致线粒体聚集在微管正末端，并最终导致线粒体功能衰竭。
Parkinson's disease has been linked to altered mitochondrial function. Mutations in Parkin (park), the Drosophila ortholog of a human gene that is responsible for many familial cases of Parkinson's disease, shorten life span, abolish fertility and disrupt mitochondrial structure. However, the role played by Park in mitochondrial function remains unclear. Here,we describe a novel Drosophila gene, clueless (clu), which encodes a highly conserved tetratricopeptide repeat protein that is related closely to the CluA protein of Dictyostelium, Clu1 of Saccharomyces cerevisiae and to similar proteins in diverse metazoan eukaryotes from Arabidopsis to humans. Like its orthologs, loss of Drosophila clu causes mitochondria to cluster within cells. We find that strong clu mutations resemble park mutations in their effects on mitochondrial function and that the two genes interact genetically. Conversely, mitochondria in park homozygotes become highly clustered. We propose that Clu functions in a novel pathway that positions mitochondria within the cell based on their physiological state. Disruption of the Clu pathway may enhance oxidative damage, alter gene expression, cause mitochondria to cluster at microtubule plus ends, and lead eventually to mitochondrial failure.