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 O2•- and H 2O2 production abrogated by inhibition of complex I. No change in the glutathione-based redox buffering was, however, observed.

Mitochondrial respiratory dysfunction in familiar parkinsonism associated with PINK1 mutation

C. PICCOLI;SARDANELLI A. M.;S. SCACCO;D. BOFFOLI;
2008-01-01

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 O2•- and H 2O2 production abrogated by inhibition of complex I. No change in the glutathione-based redox buffering was, however, observed.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/80653
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 43
  • Scopus 94
  • ???jsp.display-item.citation.isi??? 86
social impact