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

Michael Morcos, Xueliang Du, Friederike Pfisterer, Harald Hutter, Ahmed A.R. Sayed, Paul Thornalley, Naila Ahmed, John Baynes, Suzanne Thorpe, Georgi Kukudov, Andreas Schlotterer, Farastuk Bozorgmehr, Randa Abd El Baki, David Stern, Frank Moehrlen, Youssef Ibrahim, Dimitrios Oikonomou, Andreas Hamann, Christian Becker, Martin ZeierVedat Schwenger, Nexhat Miftari, Per Humpert, Hans Peter Hammes, Markus Buechler, Angelika Bierhaus, Michael Brownlee, Peter P. Nawroth

Research output: Contribution to journalArticle

197 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)260-269
Number of pages10
JournalAging cell
Volume7
Issue number2
DOIs
StatePublished - Apr 1 2008

Keywords

  • Advanced Glycation Endproducts
  • Aging
  • C. elegans
  • Glyoxalase-1
  • Lifespan
  • Metabolicrate
  • Mitochondria
  • Reactive oxygen species

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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  • Cite this

    Morcos, M., Du, X., Pfisterer, F., Hutter, H., Sayed, A. A. R., Thornalley, P., Ahmed, N., Baynes, J., Thorpe, S., Kukudov, G., Schlotterer, A., Bozorgmehr, F., El Baki, R. A., Stern, D., Moehrlen, F., Ibrahim, Y., Oikonomou, D., Hamann, A., Becker, C., ... Nawroth, P. P. (2008). Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. Aging cell, 7(2), 260-269. https://doi.org/10.1111/j.1474-9726.2008.00371.x