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 Laboratory evaluation of estrogen metabolism - Estrogen Metabolism
28/11/2011 06:53:08

Higher levels of estradiol (E2), and especially estrone (E1), in serum and urine have been consisten...

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 Estrogen-Like Activity of Metals in Mcf-7 Breast Cancer Cells
11/05/2011 09:42:23

The ability of metals to activate estrogen receptor- (ER) ...
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 26/11/2009 11:54:22

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-transenoyl-
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-enoylthioester
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 yeast mitochondrial leader sequence, this inferred that the protein represented a
physiologically functional mitochondrial 2-trans-enoyl-thioester reductase. In accordance with published findings, RNAimediated
knockdown of mecr-1 in C. elegans resulted in life span extension, presumably due to mitochondrial dysfunction.
Moreover, old mecr-1(RNAi) worms had better internal organ appearance and were more mobile than control worms,
indicating a reduced physiological age. This is the first report on RNAi work dedicated specifically to curtailing mitochondrial
FASII in metazoans. The availability of affected survivors will help to position C. elegans as an excellent model for future
pursuits in the emerging field of mitochondrial FASII research.

Citation: Gurvitz A (2009) 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. PLoS ONE 4(11): e7791. doi:10.1371/journal.pone.0007791

Editor: Alfred Lewin, University of Florida, United States of America

Received July 8, 2009; Accepted October 19, 2009; Published November 16, 2009


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