Increasing mitochondrial superoxide dismutase abundance leads to impairments in protein quality control and ROS scavenging systems and to lifespan shortening.
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'.
Zintel
Sandra
S
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.
Schwitalla
Denise
D
Luce
Karin
K
Hamann
Andrea
A
Osiewacz
Heinz D
HD
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*
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