title: Overexpression of the alternative oxidase restores senescence and fertility in a long-lived respiration-deficient mutant of Podospora anserina.
abstract: Several lines of evidence have implicated reactive oxygen species (ROS) in the pathogenesis of various degenerative diseases and in organismal ageing. Furthermore, it has been shown recently that the alternative pathway respiration present in plants lowers ROS mitochondrial production. An alternative oxidase (AOXp) also occurs in the filamentous fungus Podospora anserina. We show here that overexpression of this oxidase does not decrease ROS production and has no effect on longevity, mitochondrial stability or ageing in this fungus. In the same way, inactivation of the gene has no effect on these parameters. In contrast, overexpression of the alternative oxidase in the long-lived cox5::BLE mutant, deficient in cytochrome c oxidase, considerably increases ROS production of the mutant. It rescues slow growth rate and female sterility, indicating an improved energy level. This overexpression also restores senescence and mitochondrial DNA instability, demonstrating that these parameters are controlled by the energy level and not by the expression level of the alternative oxidase. We also suggest that expression of this oxidase in organisms naturally devoid of it could rescue respiratory defects resulting from cytochrome pathway dysfunctions.
authors.affiliation: Centre de Génétique Moléculaire -- Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: S
authors.initials: S
authors.lastname: Lorin
authors.forename: E
authors.initials: E
authors.lastname: Dufour
authors.forename: J
authors.initials: J
authors.lastname: Boulay
authors.forename: O
authors.initials: O
authors.lastname: Begel
authors.forename: S
authors.initials: S
authors.lastname: Marsy
authors.forename: A
authors.initials: A
authors.lastname: Sainsard-Chanet
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D003576:Electron Transport Complex IV / Q000235:genetics; D005298:Fertility; D008928:Mitochondria / Q000201:enzymology; D024101:Mitochondrial Proteins; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D010101:Oxygen Consumption / Q000235:genetics; D010940:Plant Proteins; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism; D017384:Sequence Deletion; D020037:Sordariales / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D000099188:Alternative Oxidase
chemical_list: D017931:DNA Primers; D003576:Electron Transport Complex IV; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D000099188:Alternative Oxidase