1. Food derived respiratory complex I inhibitors modify the effect of Leber hereditary optic neuropathy mutations.
- Author
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López-Gallardo E, Emperador S, Hernández-Ainsa C, Montoya J, Bayona-Bafaluy MP, and Ruiz-Pesini E
- Subjects
- Apoptosis drug effects, Capsaicin pharmacology, Cell Line, DNA, Mitochondrial genetics, Electron Transport Complex I metabolism, Furans pharmacology, Gene-Environment Interaction, Humans, Oxidative Phosphorylation, Oxygen Consumption drug effects, Rotenone pharmacology, Electron Transport Complex I antagonists & inhibitors, Enzyme Inhibitors pharmacology, Food Analysis, Optic Atrophy, Hereditary, Leber genetics, Point Mutation, Xenobiotics toxicity
- Abstract
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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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