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 language | English (US) |
|---|---|
| Pages (from-to) | 260-269 |
| Number of pages | 10 |
| Journal | Aging Cell |
| Volume | 7 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 2008 |
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Keywords
- Advanced Glycation Endproducts
- Aging
- C. elegans
- Glyoxalase-1
- Lifespan
- Metabolicrate
- Mitochondria
- Reactive oxygen species
ASJC Scopus subject areas
- Cell Biology
Cite this
Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. / Morcos, Michael; Du, Xue-Liang; 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, 04.2008, p. 260-269.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans
AU - Morcos, Michael
AU - Du, Xue-Liang
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
Y1 - 2008/4
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.
KW - Advanced Glycation Endproducts
KW - Aging
KW - C. elegans
KW - Glyoxalase-1
KW - Lifespan
KW - Metabolicrate
KW - Mitochondria
KW - Reactive oxygen species
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
C2 - 18221415
AN - SCOPUS:40549129694
VL - 7
SP - 260
EP - 269
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 2
ER -