title: Mitochondrial respiratory dysfunction in familiar parkinsonism associated with PINK1 mutation.
abstract: In the present study mitochondrial respiratory function of fibroblasts from a patient affected by early-onset parkinsonism carrying the homozygous W437X nonsense mutation in the PINK1 gene has been thoroughly characterized. When compared with normal fibroblasts, the patient's fibroblast mitochondria exhibited a lower respiratory activity and a decreased respiratory control ratio with cellular ATP supply relying mainly on enhanced glycolytic production. The quantity, specific activity and subunit pattern of the oxidative phosphorylation complexes were normal. However, a significant decrease of the cellular cytochrome c content was observed and this correlated with a reduced cytochrome c oxidase in situ-activity. Measurement of ROS revealed in mitochondria of the patient's fibroblasts enhanced O(2)(*-) and H(2)O(2) production abrogated by inhibition of complex I. No change in the glutathione-based redox buffering was, however, observed.
authors.affiliation: Department of Biomedical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Piccoli
authors.forename: Annamaria
authors.initials: A
authors.lastname: Sardanelli
authors.forename: Rosella
authors.initials: R
authors.lastname: Scrima
authors.forename: Maria
authors.initials: M
authors.lastname: Ripoli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarato
authors.forename: Annamaria
authors.initials: A
authors.lastname: D'Aprile
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellomo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scacco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Arcangela
authors.initials: A
authors.lastname: Iuso
authors.forename: Domenico
authors.initials: D
authors.lastname: Boffoli
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Capitanio
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D010085:Oxidative Phosphorylation; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011494:Protein Kinases / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000255:Adenosine Triphosphate; D045304:Cytochromes c; D005978:Glutathione; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D000099202:PTEN-Induced Putative Kinase