Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans
. (2008) Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. Aging Cell, Vol.7 (No.2). pp. 260-269. ISSN 1474-9726 Full text not available from this repository.
Official URL: http://dx.doi.org/10.1111/j.1474-9726.2008.00371.x
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.
|Item Type:||Journal Article|
|Subjects:||R Medicine > R Medicine (General)|
|Divisions:||Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||Aging Cell|
|Publisher:||Wiley-Blackwell Publishing Ltd.|
|Official Date:||April 2008|
|Page Range:||pp. 260-269|
|Access rights to Published version:||Restricted or Subscription Access|
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