title: Alteration of ROS homeostasis and decreased lifespan in S. cerevisiae elicited by deletion of the mitochondrial translocator FLX1.
abstract: This paper deals with the control exerted by the mitochondrial translocator FLX1, which catalyzes the movement of the redox cofactor FAD across the mitochondrial membrane, on the efficiency of ATP production, ROS homeostasis, and lifespan of S. cerevisiae. The deletion of the FLX1 gene resulted in respiration-deficient and small-colony phenotype accompanied by a significant ATP shortage and ROS unbalance in glycerol-grown cells. Moreover, the flx1Δ strain showed H2O2 hypersensitivity and decreased lifespan. The impaired biochemical phenotype found in the flx1Δ strain might be justified by an altered expression of the flavoprotein subunit of succinate dehydrogenase, a key enzyme in bioenergetics and cell regulation. A search for possible cis-acting consensus motifs in the regulatory region upstream SDH1-ORF revealed a dozen of upstream motifs that might respond to induced metabolic changes by altering the expression of Flx1p. Among these motifs, two are present in the regulatory region of genes encoding proteins involved in flavin homeostasis. This is the first evidence that the mitochondrial flavin cofactor status is involved in controlling the lifespan of yeasts, maybe by changing the cellular succinate level. This is not the only case in which the homeostasis of redox cofactors underlies complex phenotypical behaviours, as lifespan in yeasts.
authors.affiliation: Istituto di Biomembrane e Bioenergetica, CNR, Via Amendola 165/A, 70126 Bari, Italy.
authors.forename: Teresa Anna
authors.initials: TA
authors.lastname: Giancaspero
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari "A. Moro", Via Orabona 4, 70126 Bari, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Dipalo
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari "A. Moro", Via Orabona 4, 70126 Bari, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Miccolis
authors.affiliation: Institute of Molecular Biosciences, Goethe University Frankfurt, Max-von-Laue Straße 9, 60438 Frankfurt am Main, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Boles
authors.affiliation: Dipartimento di Fisica, Via P. Giuria 1, 10125 Torino, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caselle
authors.affiliation: Istituto di Biomembrane e Bioenergetica, CNR, Via Amendola 165/A, 70126 Bari, Italy ; Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari "A. Moro", Via Orabona 4, 70126 Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Barile
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis / Q000187:drug effects; D001483:Base Sequence; D004138:Dinitrocresols / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D017353:Gene Deletion; D005980:Glutathione Reductase / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006861:Hydrogen Peroxide; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs / Q000235:genetics; D010084:Oxidation-Reduction / Q000187:drug effects; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013104:Spheroplasts / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D004138:Dinitrocresols; C098870:FLX1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C024132:4,6-dinitro-o-cresol; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D005980:Glutathione Reductase