Li Han, Guo Ming
UCLA ACCESS Graduate Program and Department of Neurology, David Geffen School of Medicine and Molecular Biology Institute, University of California-Los Angeles, 695 Charles Young Drive South, Los Angeles, CA 90095, USA
J Clin Invest. 2009 Mar;119(3):442-5. doi: 10.1172/jci38619.
Mutations in the genes PTEN-induced putative kinase 1 (PINK1), PARKIN,and DJ-1 cause autosomal recessive forms of Parkinson disease (PD), and the Pink1/Parkin pathway regulates mitochondrial integrity and function.An important question is whether the proteins encoded by these genes function to regulate activities of other cellular compartments. A study in mice,reported by Xiong et al. in this issue of the JCI, demonstrates that Pink1,Parkin, and DJ-1 can form a complex in the cytoplasm, with Pink1 and DJ-1 promoting the E3 ubiquitin ligase activity of Parkin to degrade substrates via the proteasome. This protein complex in the cytosol may or may not be related to the role of these proteins in regulating mitochondrial function or oxidative stress in vivo.
基因PTEN诱导的假定激酶1（PINK1）、帕金蛋白（PARKIN）和DJ-1的突变会导致常染色体隐性帕金森病（PD），并且Pink1/帕金蛋白信号通路调节线粒体的完整性和功能。一个重要的问题是这些基因编码的蛋白质是否在调节其他细胞区室的活性中发挥作用。熊等人在本期《临床研究杂志》上发表的一项小鼠研究表明，Pink1、帕金蛋白和DJ-1可在细胞质中形成复合物，其中Pink1和DJ-1促进帕金蛋白的E3泛素连接酶活性，以通过蛋白酶体降解底物。细胞质中的这种蛋白质复合物可能与这些蛋白质在体内调节线粒体功能或氧化应激中的作用有关，也可能无关。
