title: A novel mtDNA mutation in the ATPase6 gene studied by E. coli modeling.
abstract: This study aimed to understand the pathogenesis of a new mtDNA-related etiology of Leigh syndrome. We identified the T9176G mutation as the molecular basis of Leigh syndrome in a child and looked for alterations in cellular ATP production. We then modeled the new mtDNA mutation in E. coli and analyzed ATP synthesis, hydrolysis, and the ability of the mutated enzyme to pump protons. Our results suggest that the T9176G change results in a novel, fully assembled enzyme which inhibits the holoenzyme probably by blocking the proton pathway.
authors.affiliation: Department of Molecular Medicine and Neurology, IRCCS Bambino Gesù, I-00165 Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Carrozzo
authors.forename: J
authors.initials: J
authors.lastname: Murray
authors.forename: O
authors.initials: O
authors.lastname: Capuano
authors.forename: A
authors.initials: A
authors.lastname: Tessa
authors.forename: G
authors.initials: G
authors.lastname: Chichierchia
authors.forename: M R
authors.initials: MR
authors.lastname: Neglia
authors.forename: R A
authors.initials: RA
authors.lastname: Capaldi
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000235:genetics*; D001921:Brain / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D005260:Female; D005796:Genes / Q000235:genetics; D006801:Humans; D007888:Leigh Disease / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008957:Models, Genetic; D017354:Point Mutation / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases