1. Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins
- Author
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Vadim N. Gladyshev, Maxim V. Gerashchenko, Michel B. Toledano, Inge Seim, Jean Labarre, Alaattin Kaya, Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Physiologie et Pathogénicité des Stress (PEPS), Département Biologie des Génomes (DBG), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Stress Oxydatif et Cancer (SOC), Département Biologie Cellulaire (BioCell), Physiologie et Pathogénicité des Stress ( PEPS ), Département Biologie des Génomes ( DBG ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie et de Technologies de Saclay ( IBITECS ), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire Stress Oxydants et Cancer ( LSOC ), and Département Biologie Cellulaire ( BioCell )
- Subjects
MESH : Chromosomes, Fungal ,[SDV]Life Sciences [q-bio] ,MESH : Peroxidases ,MESH : Saccharomyces cerevisiae ,Gene Dosage ,MESH : Reactive Oxygen Species ,Antimycin A ,MESH : Gene Deletion ,MESH: Oligomycins ,Mitochondrion ,MESH: Heat-Shock Proteins ,medicine.disease_cause ,MESH : Aneuploidy ,MESH : Antimycin A ,MESH: Gene Dosage ,MESH : Rotenone ,MESH: Peroxidases ,thiol peroxidase ,0302 clinical medicine ,MESH: Saccharomyces cerevisiae Proteins ,oxidative stress ,MESH : Gene Dosage ,Oxidoreductases Acting on Sulfur Group Donors ,MESH : Oligomycins ,MESH : Adaptation, Physiological ,Heat-Shock Proteins ,MESH : Electron Transport ,2. Zero hunger ,chemistry.chemical_classification ,0303 health sciences ,Multidisciplinary ,Dosage compensation ,biology ,Cytochrome c peroxidase ,MESH: Mitochondrial Proteins ,MESH: Reactive Oxygen Species ,Biological Sciences ,MESH: Saccharomyces cerevisiae ,MESH: Chromosomes, Fungal ,Adaptation, Physiological ,Biochemistry ,Peroxidases ,MESH: Hydrogen Peroxide ,MESH: Membrane Proteins ,MESH: Oxidoreductases Acting on Sulfur Group Donors ,Chromosome Deletion ,Chromosomes, Fungal ,Peroxidase ,Saccharomyces cerevisiae Proteins ,Cellular respiration ,MESH: Chromosome Deletion ,Saccharomyces cerevisiae ,Genes, Fungal ,MESH : Saccharomyces cerevisiae Proteins ,Electron Transport ,Mitochondrial Proteins ,03 medical and health sciences ,Rotenone ,medicine ,MESH: Aneuploidy ,MESH : Cytochrome-c Peroxidase ,MESH: Cytochrome-c Peroxidase ,MESH: Electron Transport ,MESH : Mitochondrial Proteins ,030304 developmental biology ,Reactive oxygen species ,[ SDV ] Life Sciences [q-bio] ,Membrane Proteins ,Hydrogen Peroxide ,MESH : Heat-Shock Proteins ,Cytochrome-c Peroxidase ,biology.organism_classification ,MESH : Chromosome Deletion ,Aneuploidy ,MESH: Adaptation, Physiological ,MESH : Oxidoreductases Acting on Sulfur Group Donors ,chemistry ,MESH : Membrane Proteins ,MESH: Gene Deletion ,biology.protein ,Oligomycins ,MESH : Genes, Fungal ,MESH : Hydrogen Peroxide ,MESH: Rotenone ,MESH: Antimycin A ,MESH: Genes, Fungal ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress ,respiration ,Gene Deletion - Abstract
International audience; Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (∆8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent ∆8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H2O2. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of ∆8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) and UTH1, present on chromosome XI. Coexpression of these genes in ∆8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation of CCP1 and UTH1 via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress.
- Published
- 2015
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