title: Metabolic and environmental conditions determine nuclear genomic instability in budding yeast lacking mitochondrial DNA.
abstract: Mitochondrial dysfunctions are an internal cause of nuclear genome instability. Because mitochondria are key regulators of cellular metabolism, we have investigated a potential link between external growth conditions and nuclear chromosome instability in cells with mitochondrial defects. Using Saccharomyces cerevisiae, we found that cells lacking mitochondrial DNA (rho0 cells) have a unique feature, with nuclear chromosome instability that occurs in nondividing cells and strongly fluctuates depending on the cellular environment. Calorie restriction, lower growth temperatures, growth at alkaline pH, antioxidants (NAC, Tiron), or presence of nearby wild-type cells all efficiently stabilize nuclear genomes of rho0 cells, whereas high glucose and ethanol boost instability. In contrast, other respiratory mutants that still possess mitochondrial DNA (RHO(+)) keep fairly constant instability rates under the same growth conditions, like wild-type or other RHO(+) controls. Our data identify mitochondrial defects as an important driver of nuclear genome instability influenced by environmental factors.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier UMR 5535 CNRS, 1919 route de Mende, 34293 Montpellier cedex 5, France.
authors.forename: Léon
authors.initials: L
authors.lastname: Dirick
authors.forename: Walid
authors.initials: W
authors.lastname: Bendris
authors.forename: Vincent
authors.initials: V
authors.lastname: Loubiere
authors.forename: Thierry
authors.initials: T
authors.lastname: Gostan
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Gueydon
authors.forename: Etienne
authors.initials: E
authors.lastname: Schwob
mesh_terms: D050539:3-Isopropylmalate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D042822:Genomic Instability; D006863:Hydrogen-Ion Concentration; D008928:Mitochondria / Q000235:genetics*; D018384:Oxidative Stress; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013696:Temperature
chemical_list: D026923:Amino Acid Transport Systems, Basic; C502212:CAN1 protein, S cerevisiae; D004272:DNA, Mitochondrial; D029701:Saccharomyces cerevisiae Proteins; C554167:URA3 protein, S cerevisiae; D050539:3-Isopropylmalate Dehydrogenase; C524993:LEU2 protein, S cerevisiae; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae
keywords: calorie restriction; membrane potential; metabolism; mitochondrial DNA; nuclear genome instability