title: Copper-modulated gene expression and senescence in the filamentous fungus Podospora anserina.
abstract: We have previously shown that the control of cellular copper homeostasis by the copper-modulated transcription factor GRISEA has an important impact on the phenotype and lifespan of Podospora anserina. Here we demonstrate that copper depletion leads to the induction of an alternative respiratory pathway and to an increase in lifespan. This response compensates mitochondrial dysfunctions via the expression of PaAox, a nuclear gene coding for an alternative oxidase. It resembles the retrograde response in Saccharomyces cerevisiae. In P. anserina, this pathway appears to be induced by specific impairments of the copper-dependent cytochrome c oxidase. It is not induced as the result of a general decline of mitochondrial functions during senescence. We cloned and characterized PaAox. Transcript levels are decreased when cellular copper, superoxide, and hydrogen peroxide levels are raised. Copper also controls transcript levels of PaSod2, the gene encoding the mitochondrial manganese superoxide dismutase (PaSOD2). PaSod2 is a target of transcription factor GRISEA. During the senescence of wild-type strain s, the activity of PaSOD2 decreases, whereas the activity of the cytoplasmic copper/zinc superoxide dismutase (PaSOD1) increases. Collectively, the data explain the postponed senescence of mutant grisea as a defined consequence of copper depletion, ultimately leading to a reduction of oxidative stress. Moreover, they suggest that during senescence of the wild-type strain, copper is released from mitochondria. The involved mechanism is unknown. However, it is striking that the permeability of mitochondrial membranes in animal systems changes during apoptosis and that mitochondrial proteins with an important impact on this type of cellular death are released.
authors.affiliation: Botanisches Institut, Johann Wolfgang Goethe-Universität, D-60439 Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Borghouts
authors.forename: A
authors.initials: A
authors.lastname: Werner
authors.forename: T
authors.initials: T
authors.lastname: Elthon
authors.forename: H D
authors.initials: HD
authors.lastname: Osiewacz
mesh_terms: D000595:Amino Acid Sequence; D019069:Cell Respiration; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005658:Fungi / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005800:Genes, Fungal / Q000235:genetics; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010269:Paraquat / Q000494:pharmacology; D010940:Plant Proteins; D011190:Potassium Cyanide / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012457:Salicylamides / Q000494:pharmacology; D016415:Sequence Alignment; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099188:Alternative Oxidase
chemical_list: D003300:Copper; D003576:Electron Transport Complex IV; D005656:Fungal Proteins; D006861:Hydrogen Peroxide; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010269:Paraquat; D010940:Plant Proteins; D011190:Potassium Cyanide; D012333:RNA, Messenger; D012457:Salicylamides; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099188:Alternative Oxidase; C101526:GRISEA protein, Podospora anserina; C005703:salicylhydroxamic acid