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

作者：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

来源：AGING CELL, 2008, 7(2): 260-269.

DOI：10.1111/j.1474-9726.2008.00371.x

• aging
• lifespan
• C
• elegans
• Advanced Glycation Endproducts
• mitochondria
• metabolic rate
• reactive oxygen species
• glyoxalase-1

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.

• 出版日期2008-4
• 单位河北医科大学