title: R492X mutation in PTEN-induced putative kinase 1 induced cellular mitochondrial dysfunction and oxidative stress.
abstract: The identification of rare monogenic forms of Parkinson's disease (PD) has provided tremendous insights into the molecular pathogenesis of the disorder. Mitochondrial dysfunction and oxidative stress are thought to play a prominent role in the pathogenesis of PD, but how the monogenic mutation gene causes the disease onset or progression is largely unknown. In this study we investigated the effects of wild-type and R492X mutation in the PTEN-induced putative kinase 1 (PINK1). Cell cultures show that R492X PINK1 mutation induces the generation of cellular reactive oxidative species (ROS), degrades cell membrane potential, causes cytochrome C (Cyt.C) release from mitochondrial to cytoplasm, attenuates mitochondrial complex I activity, and lastly, causes changes in mitochondrial numbers and morphology; especially when cells are treated with 1-Methyl-4-phenylpyridinium ion (MPP(+)). Our results suggest that the R492X mutation can cause mitochondrial dysfunction and oxidative stress and can associate with MPP(+) to induce mitochondrial dysfunction and oxidative stress.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Xiang-Li
authors.initials: XL
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, Beijing, 100101, PR China; Institute of Molecular Neurobiology, Hebei Normal University, Shijiazhuang 050016, PR China.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Shi
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Zhi-Qian
authors.initials: ZQ
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Xin-Xiang
authors.initials: XX
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, Beijing, 100101, PR China. Electronic address: zhaobl@sun5.ibp.ac.cn.
authors.forename: Bao-Lu
authors.initials: BL
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; National Laboratory of Medical Genetics of China, Changsha, Hunan 410008, PR China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan 410008, PR China. Electronic address: bstang7398@yahoo.com.cn.
authors.forename: Bei-Sha
authors.initials: BS
authors.lastname: Tang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology* / Q000235:genetics; D005333:Fetus; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics* / Q000502:physiology; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D015655:1-Methyl-4-phenylpyridinium; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D000099202:PTEN-Induced Putative Kinase