DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7
DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7
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DOI：
10.1111/cge.12841
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发表时间：
2017-07-01
影响因子：
3.5
通讯作者：
Silvestri, G.
中科院分区：
文献类型：
--
作者：
Di Nottia, M.;Masciullo, M.;Silvestri, G.
DJ-1突变与早发性帕金森病有关，约占遗传形式的1-2%。该蛋白质参与许多生物过程，其在线粒体调节中的作用引起了极大的兴趣，即使其在线粒体中的功能仍不清楚。我们描述了一名47岁的女性，患有多系统疾病，其特征为进行性早发性帕金森综合征加远端脊髓性肌萎缩、白内障和感觉神经性耳聋，与DJ-1中的一种新型纯合c.461C>A [p.T154K]突变相关。患者培养的成纤维细胞显示低ATP合成、高ROS水平和线粒体复合物I的一些亚基的量减少;氧化应激的生物标志物也导致患者血液异常。多系统参与的临床模式和我们患者的生化结果突出了DJ-1在调节线粒体对氧化应激反应中的作用。
DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.