Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration

BMC Res Notes. 2011 Dec 22:4:557. doi: 10.1186/1756-0500-4-557.

Abstract

Background: 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.

Methods: We evaluated the effect of idebenone in fibroblasts from LHON patients using enzymatic and polarographic measurements.

Results: 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.

Conclusion: 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.