title: The antioxidant Trolox helps recovery from the familial Parkinson's disease-specific mitochondrial deficits caused by PINK1- and DJ-1-deficiency in dopaminergic neuronal cells.
abstract: The nature of mitochondrial dysfunction in dopaminergic neurons in familial Parkinson's disease (PD) is unknown. We characterized the pathophenotypes of dopaminergic neuronal cells that were deficient in PINK1 or DJ-1, genes with mutations linked to familial PD. Both PINK1- and DJ-1-deficient dopaminergic neurons had the increased production of ROS, severe mitochondrial structural damages and complex I deficits. A striking decrease in complex IV activity was also prominent by the PINK1-deficiency. The complex I deficits were relatively PD-specific and were significantly improved by an antioxidant Trolox. These data suggest that mitochondrial deficits are severe in dopaminergic neurons in familial PD and antioxidant-mediated functional recovery is feasible.
authors.affiliation: Department of Brain & Cognitive Sciences, College of Pharmacy, Brain Disease Research Institute, Ewha Womans University, Seoul, South Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Shim
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yoon
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Han
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Ha
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Hyun
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Paek
authors.forename: Un Jung
authors.initials: UJ
authors.lastname: Kang
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhuang
authors.forename: Jin H
authors.initials: JH
authors.lastname: Son
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D002950:Citrate (si)-Synthase / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D057075:Enzyme Assays; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000255:Adenosine Triphosphate; D000975:Antioxidants; D018834:Chaperonin 60; D002839:Chromans; D002950:Citrate (si)-Synthase; D015786:Cytochromes b5; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase; C105131:PARK7 protein, human; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid