Research Paper Volume 2, Issue 12 pp 969—980
Modulation of the glyoxalase system in the aging model Podospora anserina: effects on growth and lifespan
- 1 Faculty for Biosciences & Cluster of Excellence Macromolecular Complexes, Molecular Developmental Biology, Goethe University, D-60438 Frankfurt am Main, Germany
- 2 Section Molecular Neurogenetics, Dept. Neurology, Goethe University Medical School, D-60590 Frankfurt am Main, Germany
received: December 15, 2010 ; accepted: December 28, 2010 ; published: December 30, 2010 ;https://doi.org/10.18632/aging.100251
How to Cite
The eukaryotic glyoxalase system consists of two enzymatic components, glyoxalase I (lactoylglutathione lyase) and glyoxalase II (hydroxyacylglutathione hydrolase). These enzymes are dedicated to the removal of toxic α-oxoaldehydes like methylglyoxal (MG). MG is formed as a by-product of glycolysis and MG toxicity results from its damaging capability leading to modifications of proteins, lipids and nucleic acids. An efficient removal of MG appears to be essential to ensure cellular functionality and viability. Here we study the effects of the genetic modulation of genes encoding the components of the glyoxalase system in the filamentous ascomycete and aging model Podospora anserina. Overexpression of PaGlo1 leads to a lifespan reduction on glucose rich medium, probably due to depletion of reduced glutathione. Deletion of PaGlo1 leads to hypersensitivity against MG added to the growth medium. A beneficial effect on lifespan is observed when both PaGlo1 and PaGlo2 are overexpressed and the corresponding strains are grown on media containing increased glucose concentrations. Notably, the double mutant has a ‘healthy’ phenotype without physiological impairments. Moreover, PaGlo1/PaGlo2_OEx strains are not long-lived on media containing standard glucose concentrations suggesting a tight correlation between the efficiency and capacity to remove MG within the cell, the level of available glucose and lifespan. Overall, our results identify the up-regulation of both components of the glyoxalase system as an effective intervention to increase lifespan in P. anserina.