http://www.cnr.it/ontology/cnr/individuo/prodotto/ID38648
Respiratory Complex I Dysfunction Due to Mitochondrial DNA Mutations Shifts the Voltage Threshold for Opening of the Permeability Transition Pore toward Resting Levels. (Articolo in rivista)
- Type
- Label
- Respiratory Complex I Dysfunction Due to Mitochondrial DNA Mutations Shifts the Voltage Threshold for Opening of the Permeability Transition Pore toward Resting Levels. (Articolo in rivista) (literal)
- Anno
- 2009-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1074/jbc.M807321200 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Porcelli A.M.; Angelin A.; Ghelli A.; Mariani E.; Martinuzzi A.; Carelli V.; Petronilli V.; Bernardi P.; Rugolo M. (literal)
- Pagina inizio
- Pagina fine
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Departments of Evolutionary and Experimental Biology and Neurological Sciences, University of Bologna, 40126 Bologna; Istituto di Ricovero e Cura a Carattere Scientifico \"E. Medea\", Conegliano Veneto, and CNR Institute of Neuroscience and Department of Biomedical Sciences, University of Padova, Italy (literal)
- Titolo
- Respiratory Complex I Dysfunction Due to Mitochondrial DNA Mutations Shifts the Voltage Threshold for Opening of the Permeability Transition Pore toward Resting Levels. (literal)
- Abstract
- We have studied mitochondrial bioenergetics in HL180 cells ( a cybrid line harboring the T14484C/ND6 and G14279A/ND6 mtDNA mutations of Leber hereditary optic neuropathy, leading to an similar to 50% decrease of ATP synthesis) and XTC.UC1 cells ( derived from a thyroid oncocytoma bearing a disruptive frame-shift mutation in MT-ND1, which impairs complex I assembly). The addition of rotenone to HL180 cells and of antimycin A to XTC.UC1 cells caused fast mitochondrial membrane depolarization that was prevented by treatment with cyclosporin A, intracellular Ca(2+) chelators, and antioxidant. Both cell lines also displayed an anomalous response to oligomycin, with rapid onset of depolarization that was prevented by cyclosporin A and by overexpression of Bcl-2. These findings indicate that depolarization by respiratory chain inhibitors and oligomycin was due to opening of the mitochondrial permeability transition pore (PTP). A shift of the threshold voltage for PTP opening close to the resting potential may therefore be the underlying cause facilitating cell death in diseases affecting complex I activity. This study provides a unifying reading frame for previous observations on mitochondrial dysfunction, bioenergetic defects, and Ca(2+) deregulation in mitochondrial diseases. Therapeutic strategies aimed at normalizing the PTP voltage threshold may be instrumental in ameliorating the course of complex I-dependent mitochondrial diseases. (literal)
- Prodotto di
- Autore CNR
- Insieme di parole chiave
Incoming links:
- Autore CNR di
- Prodotto
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
- Insieme di parole chiave di