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

Aging Cell. 2008 Mar;7(2):260-9. doi: 10.1111/j.1474-9726.2008.00371.x. Epub 2008 Jan 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins / metabolism
  • Enzyme Inhibitors
  • Feedback, Physiological
  • Gene Expression
  • Lactoylglutathione Lyase / antagonists & inhibitors
  • Lactoylglutathione Lyase / biosynthesis*
  • Lactoylglutathione Lyase / deficiency*
  • Longevity*
  • Mitochondria / enzymology*
  • Mitochondrial Proteins / metabolism
  • Mutation
  • Oxidative Phosphorylation
  • Oxidative Stress
  • Protein Modification, Translational*
  • Pyruvaldehyde / metabolism
  • RNA, Helminth
  • RNA, Messenger / analysis
  • Reactive Oxygen Species / analysis
  • Reactive Oxygen Species / metabolism


  • Caenorhabditis elegans Proteins
  • Enzyme Inhibitors
  • Mitochondrial Proteins
  • RNA, Helminth
  • RNA, Messenger
  • Reactive Oxygen Species
  • Pyruvaldehyde
  • Lactoylglutathione Lyase