Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration
1 INSERM U771, Angers 49000, France
2 CNRS 6214, Angers 49000, France
3 LUNAM Université, Angers 49000, France
4 Département de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers 49000, France
5 Département de Neurologie, Centre Hospitalier Universitaire, Angers 49000, France
6 Département d'Ophtalmologie, Centre Hospitalier Universitaire, Angers 49000, France
7 Département de Biochimie et Génétique, CHU d'Angers, 49933 Angers, France
BMC Research Notes 2011, 4:557 doi:10.1186/1756-0500-4-557Published: 22 December 2011
Leber's hereditary optic neuropathy (LHON) is caused by mutations in the complex I subunits of the respiratory chain. Although patients have been treated with idebenone since 1992, the efficacy of the drug is still a matter of debate.
We evaluated the effect of idebenone in fibroblasts from LHON patients using enzymatic and polarographic measurements.
Complex I activity was 42% greater in treated fibroblasts compared to controls (p = 0.002). Despite this complex I activity improvement, the effects on mitochondrial respiration were contradictory, leading to impairment in some cases and stimulation in others.
These results indicate that idebenone is able to compensate the complex I deficiency in LHON patient cells with variable effects on respiration, indicating that the patients might not be equally likely to benefit from the treatment.