title: DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7.
abstract: 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.
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Nottia
authors.affiliation: SPInal REhabilitation Lab, IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Masciullo
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Verrigni
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Petrillo
authors.affiliation: Institute of Neurology, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Modoni
authors.affiliation: Department of Nuclear Medicine, Università Cattolica del Sacro Cuore, Fondazione Policlinico A.Gemelli Rome, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Rizzo
authors.affiliation: Department of Nuclear Medicine, Università Cattolica del Sacro Cuore, Fondazione Policlinico A.Gemelli Rome, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Di Giuda
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Rizza
authors.affiliation: Division of Genetic Disorders and Rare Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Niceta
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Torraco
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bianchi
authors.affiliation: Department of Neuroscience, Fondazione Don Carlo Gnocchi Onlus, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Santoro
authors.affiliation: Institute of Neurology, Rome, Italy.
authors.forename: A R
authors.initials: AR
authors.lastname: Bentivoglio
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Piemonte
authors.affiliation: Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Carrozzo
authors.affiliation: Institute of Neurology, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D000071617:Protein Deglycase DJ-1 / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D042967:Electron Transport Complex I
keywords: DJ-1; early-onset parkinsonism; mitochondrial complex I; mitochondrial disease; oxidative stress