title: Increasing mitochondrial superoxide dismutase abundance leads to impairments in protein quality control and ROS scavenging systems and to lifespan shortening.
abstract: The fungal aging model Podospora anserina contains three superoxide dismutases (SODs) in different cellular compartments. While PaSOD1 represents the Cu/Zn isoform located in the cytoplasm and in the mitochondrial inter-membrane space, PaSOD2 localizes to the perinuclear ER. PaSOD3, a protein with a manganese binding domain and a mitochondrial targeting sequence (MTS) is the mitochondrial SOD. Over-expression of PaSod3 leads to lifespan reduction and increased sensitivity against paraquat and hydrogen peroxide. The negative effects of PaSod3 over-expression correlate with a strong reduction in the abundance of mitochondrial peroxiredoxin, PaPRX1, and the matrix protease PaCLPP disclosing impairments of mitochondrial quality control and ROS scavenging pathways in PaSod3 over-expressors. Deletion of PaSod3 leads to increased paraquat sensitivity while hydrogen peroxide sensitivity and lifespan are not significantly changed when compared to the wild-type strain. These latter characteristics are unexpected and challenge the 'mitochondrial free radical theory of aging'.
authors.affiliation: Institute of Molecular Biosciences and Cluster of Excellence Macromolecular Complexes, Department of Biosciences, J.W. Goethe-University, Max-von-Laue-Strasse 9, Frankfurt am Main, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zintel
authors.forename: Denise
authors.initials: D
authors.lastname: Schwitalla
authors.forename: Karin
authors.initials: K
authors.lastname: Luce
authors.forename: Andrea
authors.initials: A
authors.lastname: Hamann
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Osiewacz
mesh_terms: D001483:Base Sequence; D004271:DNA, Fungal / Q000235:genetics; D016166:Free Radical Scavengers / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005800:Genes, Fungal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D010269:Paraquat / Q000494:pharmacology; D048468:Podospora / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D016166:Free Radical Scavengers; D005656:Fungal Proteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D010269:Paraquat