title: Yeast models of mutations in the mitochondrial ATP6 gene found in human cancer cells.
abstract: Since the discovery of somatic mtDNA mutations in tumor cells, multiple studies have focused on establishing a causal relationship between those changes and alterations in energy metabolism, a hallmark of cancer cells. Yet the consequences of these mutations on mitochondrial function remain largely unknown. In this study, Saccharomyces cerevisiae has been used as a model to investigate the functional consequences of four cancer-associated missense mutations (8914C>A, 8932C>T, 8953A>G, 9131T>C) found in the mitochondrial MT-ATP6 gene. This gene encodes the a-subunit of F1FO-ATP synthase, which catalyzes the last steps of ATP production in mitochondria. Although the four studied mutations affected well-conserved residues of the a-subunit, only one of them (8932C>T) had a significant impact on mitochondrial function, due to a less efficient incorporation of the a-subunit into ATP synthase. Our findings indicate that these ATP6 genetic variants found in human tumors are neutral mitochondrial genome substitutions with a limited, if any, impact on the energetic function of mitochondria.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Niedzwiecka
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland; Institut de Biochimie et Génétique Cellulaires, CNRS UMR5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
authors.forename: Anna Magdalena
authors.initials: AM
authors.lastname: Kabala
authors.affiliation: Institut de Biochimie et Génétique Cellulaires, CNRS UMR5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Lasserre
authors.affiliation: Institut de Biochimie et Génétique Cellulaires, CNRS UMR5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Tribouillard-Tanvier
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland; Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Golik
authors.affiliation: Institut de Biochimie et Génétique Cellulaires, CNRS UMR5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Dautant
authors.affiliation: Institut de Biochimie et Génétique Cellulaires, CNRS UMR5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: di Rago
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland. Electronic address: roza@ibb.waw.pl.
authors.forename: Roza
authors.initials: R
authors.lastname: Kucharczyk
mesh_terms: D006801:Humans; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D009369:Neoplasms / Q000473:pathology; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C501004:ATP6 protein, S cerevisiae; C501005:MT-ATP6 protein, human; D029701:Saccharomyces cerevisiae Proteins; D025261:Mitochondrial Proton-Translocating ATPases
keywords: ATP synthase; Bioenergetics; Cancer; MT-ATP6; Mitochondria; mtDNA mutation