Deletion of the mitochondrial NADH kinase increases mitochondrial DNA stability and life span in the filamentous fungus Podospora anserina.
In the filamentous fungus Podospora anserina, aging is systematically associated with mitochondrial DNA (mtDNA) instability. A causal link between deficiency of the cytochrome respiratory pathway and lifespan extension has been demonstrated. Knock out of the cytochrome respiratory pathway induces the expression of an alternative oxidase and is associated with a reduction in free radical production. The question of the links between mtDNA stability, ROS generation and lifespan is therefore clearly raised in this organism. NADPH lies at the heart of many anti-oxidant defenses of the cell. In Saccharomyces cerevisiae, the mitochondrial NADPH is largely provided by the Pos5 NADH kinase. We show here that disruption of PaNdk1 encoding the potential mitochondrial NADH kinase of P. anserina leads to severe somatic and sexual defects and to hypersensitivity to hydrogen peroxide and paraquat. Surprisingly, it also leads to a spectacular increase of mtDNA stability and lifespan. We propose that an adaptative metabolic change including the induction of the alternative oxidase can account for these results.
El-Khoury
Riyad
R
Centre National de la Recherche Scientifique, Centre de Génétique Moléculaire, Gif-sur-Yvette, France.
Sainsard-Chanet
Annie
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005800:Genes, Fungal; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D048468:Podospora / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013481:Superoxides / Q000378:metabolism
D017931:DNA Primers; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D009243:NAD; D013481:Superoxides; D017853:Phosphotransferases (Alcohol Group Acceptor); C060670:POS5 protein, S cerevisiae