We have cloned and functionally characterized an Na+-coupled citrate transporter from Caenorhabditis elegans (ceNAC-2). This transporter shows significant sequence homology to Drosophila Indy and the mammalian Na+-coupled citrate transporter NaCT (now known as NaC2). When heterologously expressed in a mammalian cell line or in Xenopus oocytes, the cloned ceNAC-2 mediates the Na+-coupled transport of various intermediates of the citric acid cycle. However, it transports the tricarboxylate citrate more efficiently than dicarboxylates such as succinate, a feature different from that of ceNAC-1 (formerly known as ceNaDC1) and ceNAC-3 (formerly known as ceNaDC2). The transport process is electrogenic, as evidenced from the substrate-induced inward currents in oocytes expressing the transporter under voltage-clamp conditions. Expression studies using a reporter-gene fusion method in transgenic C. elegans show that the gene is expressed in the intestinal tract, the organ responsible for not only the digestion and absorption of nutrients but also for the storage of energy in this organism. Functional knockdown of the transporter by RNAi (RNA interference) not only leads to a significant increase in life span, but also causes a significant decrease in body size and fat content. The substrates of ceNAC-2 play a critical role in metabolic energy production and in the biosynthesis of cholesterol and fatty acids. The present studies suggest that the knockdown of these metabolic functions by RNAi is linked to an extension of life span and a decrease in fat content and body size.
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Research Article|
April 01 2004
Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size and fat content in Caenorhabditis elegans
You-Jun FEI;
You-Jun FEI
1
*Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A.
1To whom correspondence should be addressed (e-mail yjfei@mail.mcg.edu).
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Jin-Cai LIU;
Jin-Cai LIU
*Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A.
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Katsuhisa INOUE;
Katsuhisa INOUE
*Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A.
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Lina ZHUANG;
Lina ZHUANG
*Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A.
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Katsuya MIYAKE;
Katsuya MIYAKE
†Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, U.S.A.
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Seiji MIYAUCHI;
Seiji MIYAUCHI
*Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A.
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Vadivel GANAPATHY
Vadivel GANAPATHY
*Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A.
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Publisher: Portland Press Ltd
Received:
November 25 2003
Accepted:
December 16 2003
Accepted Manuscript online:
December 16 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 379 (1): 191–198.
Article history
Received:
November 25 2003
Accepted:
December 16 2003
Accepted Manuscript online:
December 16 2003
Citation
You-Jun FEI, Jin-Cai LIU, Katsuhisa INOUE, Lina ZHUANG, Katsuya MIYAKE, Seiji MIYAUCHI, Vadivel GANAPATHY; Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size and fat content in Caenorhabditis elegans. Biochem J 1 April 2004; 379 (1): 191–198. doi: https://doi.org/10.1042/bj20031807
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