Mitochondrial defect and PGC-1± dysfunction in parkin-associated familial Parkinson's disease.

Torna indietro

Abstract

Mutations in the parkin gene are expected to play an essential role in autosomal recessive Parkinson's disease. Recent studies have established an impact of parkin mutations on mitochondrial function and autophagy. In primary skin broblasts from two patients affected by an early onset Parkinson's disease, we identi ed a hitherto unreported compound heterozygous mutation del exon2-3/del exon3 in the parkin gene, leading to the complete loss of the full-length protein. In both patients, but not in their heterozygous parental control, we observed severe ultrastructural abnormalities, mainly in mitochondria. This was associated with impaired energy metabolism, deregulated reactive oxygen species (ROS) production, resulting in lipid oxidation, and peroxisomal alteration. In view of the involvement of parkin in the mitochondrial quality control system, we have investigated upstream events in the organelles' biogenesis. The expression of the peroxisome proliferator-activated receptor gamma-coactivator 1-alpha (PGC-1 ), a strong stimulator of mitochondrial biogenesis, was remarkably upregulated in both patients. However, the function of PGC-1 was blocked, as revealed by the lack of its downstream target gene induction. In conclusion, our data con rm the role of parkin in mitochondrial homeostasis and suggest a potential involvement of the PGC-1 pathway in the pathogenesis of Parkinson's disease. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.

Autore Pugliese

Tutti gli autori

  • Pacelli C.; De Rasmo D.; Signorile A.; Grattagliano I.; di Tullio G.; D'Orazio A.; Nico B.; Comi G.P.; Ronchi D.; Ferranini E.; Pirolo D.; Seibel P.; Schubert S.; Gaballo A.; Villani G.; Cocco T.

Titolo volume/Rivista

Biochimica et biophysica acta. Molecular basis of disease

Anno di pubblicazione

2011

ISSN

0925-4439

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

Non Disponibile

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile