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 Zeier & 8 others Vedat Schwenger, Nexhat Miftari, Per Humpert, Hans Peter Hammes, Markus Buechler, Angelika Bierhaus, Michael Brownlee, Peter P. Nawroth

Research output: Contribution to journalArticle

185 Citations (Scopus)

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

Fingerprint

Pyruvaldehyde
Mitochondrial Proteins
Caenorhabditis elegans
Reactive Oxygen Species
Glycolysis
Oxidative Stress
Messenger RNA
Mutation
Enzymes

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

Cite this

Morcos, M., Du, X., Pfisterer, F., Hutter, H., Sayed, A. A. R., Thornalley, P., ... 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

Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. / Morcos, Michael; Du, Xueliang; Pfisterer, Friederike; Hutter, Harald; Sayed, Ahmed A.R.; Thornalley, Paul; Ahmed, Naila; Baynes, John; Thorpe, Suzanne; Kukudov, Georgi; Schlotterer, Andreas; Bozorgmehr, Farastuk; El Baki, Randa Abd; Stern, David; Moehrlen, Frank; Ibrahim, Youssef; Oikonomou, Dimitrios; Hamann, Andreas; Becker, Christian; Zeier, Martin; Schwenger, Vedat; Miftari, Nexhat; Humpert, Per; Hammes, Hans Peter; Buechler, Markus; Bierhaus, Angelika; Brownlee, Michael; Nawroth, Peter P.

In: Aging Cell, Vol. 7, No. 2, 01.04.2008, p. 260-269.

Research output: Contribution to journalArticle

Morcos, M, Du, X, Pfisterer, F, Hutter, H, Sayed, AAR, Thornalley, P, Ahmed, N, Baynes, J, Thorpe, S, Kukudov, G, Schlotterer, A, Bozorgmehr, F, El Baki, RA, Stern, D, Moehrlen, F, Ibrahim, Y, Oikonomou, D, Hamann, A, Becker, C, Zeier, M, Schwenger, V, Miftari, N, Humpert, P, Hammes, HP, Buechler, M, Bierhaus, A, Brownlee, M & Nawroth, PP 2008, 'Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans', Aging Cell, vol. 7, no. 2, pp. 260-269. https://doi.org/10.1111/j.1474-9726.2008.00371.x
Morcos, Michael ; Du, Xueliang ; Pfisterer, Friederike ; Hutter, Harald ; Sayed, Ahmed A.R. ; Thornalley, Paul ; Ahmed, Naila ; Baynes, John ; Thorpe, Suzanne ; Kukudov, Georgi ; Schlotterer, Andreas ; Bozorgmehr, Farastuk ; El Baki, Randa Abd ; Stern, David ; Moehrlen, Frank ; Ibrahim, Youssef ; Oikonomou, Dimitrios ; Hamann, Andreas ; Becker, Christian ; Zeier, Martin ; Schwenger, Vedat ; Miftari, Nexhat ; Humpert, Per ; Hammes, Hans Peter ; Buechler, Markus ; Bierhaus, Angelika ; Brownlee, Michael ; Nawroth, Peter P. / Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. In: Aging Cell. 2008 ; Vol. 7, No. 2. pp. 260-269.
@article{d8850b1ee8154fcf922085a486bc6b6f,
title = "Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans",
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.",
author = "Michael Morcos and Xueliang Du and Friederike Pfisterer and Harald Hutter and Sayed, {Ahmed A.R.} and Paul Thornalley and Naila Ahmed and John Baynes and Suzanne Thorpe and Georgi Kukudov and Andreas Schlotterer and Farastuk Bozorgmehr and {El Baki}, {Randa Abd} and David Stern and Frank Moehrlen and Youssef Ibrahim and Dimitrios Oikonomou and Andreas Hamann and Christian Becker and Martin Zeier and Vedat Schwenger and Nexhat Miftari and Per Humpert and Hammes, {Hans Peter} and Markus Buechler and Angelika Bierhaus and Michael Brownlee and Nawroth, {Peter P.}",
year = "2008",
month = "4",
day = "1",
doi = "10.1111/j.1474-9726.2008.00371.x",
language = "English (US)",
volume = "7",
pages = "260--269",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans

AU - Morcos, Michael

AU - Du, Xueliang

AU - Pfisterer, Friederike

AU - Hutter, Harald

AU - Sayed, Ahmed A.R.

AU - Thornalley, Paul

AU - Ahmed, Naila

AU - Baynes, John

AU - Thorpe, Suzanne

AU - Kukudov, Georgi

AU - Schlotterer, Andreas

AU - Bozorgmehr, Farastuk

AU - El Baki, Randa Abd

AU - Stern, David

AU - Moehrlen, Frank

AU - Ibrahim, Youssef

AU - Oikonomou, Dimitrios

AU - Hamann, Andreas

AU - Becker, Christian

AU - Zeier, Martin

AU - Schwenger, Vedat

AU - Miftari, Nexhat

AU - Humpert, Per

AU - Hammes, Hans Peter

AU - Buechler, Markus

AU - Bierhaus, Angelika

AU - Brownlee, Michael

AU - Nawroth, Peter P.

PY - 2008/4/1

Y1 - 2008/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=40549129694&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40549129694&partnerID=8YFLogxK

U2 - 10.1111/j.1474-9726.2008.00371.x

DO - 10.1111/j.1474-9726.2008.00371.x

M3 - Article

VL - 7

SP - 260

EP - 269

JO - Aging Cell

JF - Aging Cell

SN - 1474-9718

IS - 2

ER -