4-hydroxy-25-desoxyneorollinicin and Optic-Atrophy--Hereditary--Leber

Mitochondrial DNA mutations in genes encoding respiratory complex I polypeptides can cause Leber hereditary optic neuropathy. Toxics affecting oxidative phosphorylation system can also cause mitochondrial optic neuropathy. Some complex I inhibitors found in edible plants might differentially interact with these pathologic mutations and modify their penetrance. To analyze this interaction, we have compared the effect of rotenone, capsaicin and rolliniastatin-1 on cybrids harboring the most frequent Leber hereditary optic neuropathy mutations and found that m.3460G > A mutation increases rotenone resistance but capsaicin and rolliniastatin-1 susceptibility. Thus, to explain the pathogenicity of mitochondrial diseases due to mitochondrial DNA mutations, their potential interactions with environment factors will have to be considered.

Topics: Apoptosis; Capsaicin; Cell Line; DNA, Mitochondrial; Electron Transport Complex I; Enzyme Inhibitors; Food Analysis; Furans; Gene-Environment Interaction; Humans; Optic Atrophy, Hereditary, Leber; Oxidative Phosphorylation; Oxygen Consumption; Point Mutation; Rotenone; Xenobiotics