Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans
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| Authors: | Morcos, M; Du, XL; Pfisterer, F; Hutter, H; Sayed, AAR; Thornalley, P; Ahmed, N; Baynes, J; Thorpe, S; Kukudov, G; Schlotterer, A; Bozorgmehr, F; El Baki, RA; Stern, D; Moehrlen, F; Ibrahim, Y; Oikonomou, D; Hamann, A; Becker, C; Zeier, M; Schwenger, V; Miftari, N; Humpert, P; Hammes, HP; Buechler, M; Bierhaus, A; Brownlee, M; Nawroth, PP |
| Year: | 2008 |
| Journal: | Aging Cell 7: 260-269 Article Link (DOI) |
| Title: | Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans |
| Abstract: | Studies of mutations affecting lifespan in Caenorhabditis elegans show that mitochondrial generation of reactive oxygen species (ROS) plays a major causative role in organismal aging. Here, we describe a novel mechanism for regulating mitochondrial ROS production and lifespan in C. elegans: progressive mitochondrial protein modification by the glycolysis-derived dicarbonyl metabolite methylglyoxal (MG). We demonstrate that the activity of glyoxalase-1, an enzyme detoxifying MG, is markedly reduced with age despite unchanged levels of glyoxalase-1 mRNA. The decrease in enzymatic activity promotes accumulation of MG-derived adducts and oxidative stress markers, which cause further inhibition of glyoxalase-1 expression. Over-expression of the C. elegans glyoxalase-1 orthologue CeGly decreases MG modifications of mitochondrial proteins and mitochondrial ROS production, and prolongs C. elegans lifespan. In contrast, knock-down of CeGly increases MG modifications of mitochondrial proteins and mitochondrial ROS production, and decreases C. elegans lifespan. |
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