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Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans
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. (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
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.
| Item Type: | Journal Article | ||||
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| Subjects: | R Medicine > R Medicine (General) | ||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School |
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| Journal or Publication Title: | Aging Cell | ||||
| Publisher: | Wiley-Blackwell Publishing Ltd. | ||||
| ISSN: | 1474-9726 | ||||
| Official Date: | April 2008 | ||||
| Dates: |
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| Volume: | Vol.7 | ||||
| Number: | No.2 | ||||
| Page Range: | pp. 260-269 | ||||
| Identifier: | 10.1111/j.1474-9726.2008.00371.x | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| URI: | http://wrap.warwick.ac.uk/id/eprint/45808 |
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