title: Intrinsic uncoupling of cytochrome c oxidase may cause the maternally inherited mitochondrial diseases MELAS and LHON.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, MCP/Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Mather
authors.forename: H
authors.initials: H
authors.lastname: Rottenberg
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D017241:MELAS Syndrome / Q000201:enzymology / Q000235:genetics*; D009861:Onium Compounds / Q000378:metabolism; D015418:Optic Atrophies, Hereditary / Q000201:enzymology / Q000235:genetics*; D009943:Organophosphorus Compounds / Q000378:metabolism; D010231:Paracoccus denitrificans / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D017494:Proton Pumps / Q000378:metabolism; D013772:Tetramethylphenylenediamine / Q000494:pharmacology
chemical_list: D004272:DNA, Mitochondrial; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D017494:Proton Pumps; D003576:Electron Transport Complex IV; D013772:Tetramethylphenylenediamine; D001205:Ascorbic Acid; C013289:tetraphenylphosphonium