Department of Embryology/Howard Hughes Medical Institute, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Dis Model Mech. 2009 Sep-Oct;2(9-10):490-9. doi: 10.1242/dmm.002378. Epub 2009 Jul 28.
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.
帕金森病与线粒体功能改变有关。帕金森基因（park）的突变，该基因是导致许多家族性帕金森病的人类基因的果蝇同源物，缩短了寿命，消除了生育能力并破坏了线粒体结构。但是，Park 在线粒体功能中的作用仍不清楚。在这里，我们描述了一个新的果蝇基因，clueless（clu），它编码一种高度保守的四肽重复蛋白，与 Dictyostelium 的 CluA 蛋白，酿酒酵母的 Clu1 和来自拟南芥到人类的各种后生动物真核生物的类似蛋白密切相关。像其同源物一样，果蝇 clu 的缺失导致线粒体在细胞内聚集。我们发现，强 clu 突变在对线粒体功能的影响上类似于 park 突变，并且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 在线粒体在细胞内定位的新途径中起作用，该途径基于它们的生理状态。Clu 途径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端，并最终导致线粒体衰竭。
