ascorbic-acid and tetraphenylphosphonium

Mutations in the human mtDNA gene encoding subunit III of cytochrome c oxidase (CO) have been reported to cause MELAS and LHON. Poracoccus denitrificans cells expressing substitutions homologous to these MELAS- and LHON-causing mutations had lower growth yield than wild type cells and lower efficiency of proton pumping by CO (e.g. lower H+/e ratio and lower deltapsi), but had similar CO activity. These results indicate that both substitutions (F263L > A212T) cause intrinsic uncoupling, which may be the direct cause of the diseases. These results also suggest that subunit III is involved in proton pumping.

Topics: Ascorbic Acid; DNA, Mitochondrial; Electron Transport Complex IV; Gene Deletion; Gene Expression; Humans; Kinetics; MELAS Syndrome; Onium Compounds; Optic Atrophies, Hereditary; Organophosphorus Compounds; Paracoccus denitrificans; Proton Pumps; Tetramethylphenylenediamine