Mitochondrial respiratory dysfunction in familiar parkinsonism associated with PINK1 mutation.
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.
Piccoli
Claudia
C
Department of Biomedical Sciences, University of Foggia, Foggia, Italy.
Sardanelli
Annamaria
A
Scrima
Rosella
R
Ripoli
Maria
M
Quarato
Giovanni
G
D'Aprile
Annamaria
A
Bellomo
Francesco
F
Scacco
Salvatore
S
De Michele
Giuseppe
G
Filla
Alessandro
A
Iuso
Arcangela
A
Boffoli
Domenico
D
Capitanio
Nazzareno
N
Papa
Sergio
S
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
D000255:Adenosine Triphosphate; D045304:Cytochromes c; D005978:Glutathione; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D000099202:PTEN-Induced Putative Kinase