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Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans

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Morcos, Michael, Du, Xueliang, Pfisterer, Friederike, Hutter, Harald, Sayed, Ahmed A. R., Thornalley, Paul J., Ahmed, Naila, Baynes, John, Thorpe, Suzanne, Kukudov, Georgi et al.
(2008) Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. Aging Cell, Vol.7 (No.2). pp. 260-269. doi:10.1111/j.1474-9726.2008.00371.x ISSN 1474-9726.

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Official URL: http://dx.doi.org/10.1111/j.1474-9726.2008.00371.x

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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
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: Aging Cell
Publisher: Wiley-Blackwell Publishing Ltd.
ISSN: 1474-9726
Official Date: April 2008
Dates:
DateEvent
April 2008Published
Volume: Vol.7
Number: No.2
Page Range: pp. 260-269
DOI: 10.1111/j.1474-9726.2008.00371.x
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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