title: Biochemical phenotypes associated with the mitochondrial ATP6 gene mutations at nt8993.
abstract: Two point mutations (T>G and T>C) at the same 8993 nucleotide of mitochondrial DNA (at comparable mutant load), affecting the ATPase 6 subunit of the F1F0-ATPase, result in neurological phenotypes of variable severity in humans. We have investigated mitochondrial function in lymphocytes from individuals carrying the 8993T>C mutation: the results were compared with data from five 8993T>G NARP (Neuropathy, Ataxia and Retinitis Pigmentosa) patients. Both 8993T>G and 8993T>C mutations led to energy deprivation and ROS overproduction. However, the relative contribution of the two pathogenic components is different depending on the mutation considered. The 8993T>G change mainly induces an energy deficiency, whereas the 8993T>C favours an increased ROS production. These results possibly highlight the different pathogenic mechanism generated by the two mutations at position 8993 and provide useful information to better characterize the biochemical role of the highly conserved Leu-156 in ATPase 6 subunit of the mitochondrial ATP synthase complex.
authors.affiliation: Dipartimento di Biochimica G. Moruzzi, via Irnerio 48, Università di Bologna, 40126 Bologna, and Fondazione Ospedale Maggiore IRCCS-Centro Dino Ferrari, Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baracca
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sgarbi
authors.forename: Marina
authors.initials: M
authors.lastname: Mattiazzi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Casalena
authors.forename: Eleonora
authors.initials: E
authors.lastname: Pagnotta
authors.forename: Maria L
authors.initials: ML
authors.lastname: Valentino
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lenaz
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Solaini
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001259:Ataxia / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D050259:Genes, Mitochondrial; D006801:Humans; D007888:Leigh Disease / Q000235:genetics*; D007930:Leucine / Q000737:chemistry / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D008564:Membrane Potentials; D008875:Middle Aged; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D009154:Mutation; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; C501005:MT-ATP6 protein, human; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases; D007930:Leucine