2. Academic Validation
  3. R492X mutation in PTEN-induced putative kinase 1 induced cellular mitochondrial dysfunction and oxidative stress

R492X mutation in PTEN-induced putative kinase 1 induced cellular mitochondrial dysfunction and oxidative stress

  • Brain Res. 2010 Sep 10;1351:229-237. doi: 10.1016/j.brainres.2010.06.005.
Xiang-Li Yuan 1,  Ji-Feng Guo 2,  Zhen-Hua Shi 3,  Zhi-Qian Xiao 1,  Xin-Xiang Yan 2,  Bao-Lu Zhao 4,  Bei-Sha Tang 5
Affiliations

Affiliations

  • 1 Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
  • 2 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.
  • 3 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.
  • 4 State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, Beijing, 100101, PR China. Electronic address: [email protected].
  • 5 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: [email protected].
PMID: 20547144 DOI: 10.1016/j.brainres.2010.06.005
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.

Figures