a c. elegans model for mitochondrial fatty acid synthase ii the longevity-associated gene w09h1.5mecr-1 encodes a 2-trans-enoyl-thioester reductase秀丽隐杆线虫模型线粒体脂肪酸合酶ii与长寿相关的基因w09h1.5mecr-1编码2-trans-enoyl-thioester还原酶.pdfVIP

A C. elegans Model for Mitochondrial Fatty Acid Synthase II: The Longevity-Associated Gene W09H1.5/ mecr-1 Encodes a 2-trans-Enoyl-Thioester Reductase Aner Gurvitz* Section of Physiology of Lipid Metabolism, Institute of Physiology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria Abstract Our recognition of the mitochondria as being important sites of fatty acid biosynthesis is continuously unfolding, especially in light of new data becoming available on compromised fatty acid synthase type 2 (FASII) in mammals. For example, perturbed regulation of murine 17b-HSD8 encoding a component of the mitochondrial FASII enzyme 3-oxoacyl-thioester reductase is implicated in polycystic kidney disease. In addition, over-expression in mice of the Mecr gene coding for 2-trans- enoyl-thioester reductase, also of mitochondrial FASII, leads to impaired heart function. However, mouse knockouts for mitochondrial FASII have hitherto not been reported and, hence, there is a need to develop alternate metazoan models such as nematodes or fruit flies. Here, the identification of Caenorhabditis elegans W09H1.5/MECR-1 as a 2-trans-enoyl- thioester reductase of mitochondrial FASII is reported. To identify MECR-1, Saccharomyces cerevisiae etr1D mutant cells were employed that are devoid of mitochondrial 2-trans-enoyl-thioester reductase Etr1p. These yeast mutants fail to synthesize sufficient levels of lipoic acid or form cytochrome complexes, and cannot respire or grow on non-fermentable carbon sources. A mutant yeast strain ectopically expressing nematode mecr-1 was shown to contain reductase activity and resemble the self-complemented mutant strain for these phenotype characteristics. Since MECR-1 was not intentionally targeted for compartmentalization using a