Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size and fat content in Caenorhabditis elegans
Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size and fat content in Caenorhabditis elegans
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DOI：
10.1042/bj20031807
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发表时间：
2004-04-01
影响因子：
4.1
通讯作者：
Ganapathy, V
中科院分区：
文献类型：
--
作者：
Fei, YJ;Liu, JC;Ganapathy, V
我们已经克隆和功能特征的Na+耦合柠檬酸盐转运蛋白秀丽隐杆线虫（ceNAC-2）。该转运蛋白与果蝇Indy和哺乳动物Na+偶联柠檬酸盐转运蛋白NaCT（现在称为NaC 2）具有显著的序列同源性。当在哺乳动物细胞系或Xenopas卵母细胞中异源表达时，克隆的ceNAC-2介导柠檬酸循环的各种中间体的Na-偶联转运。然而，它比二羧酸盐如琥珀酸盐更有效地转运三羧酸柠檬酸盐，这是与ceNAC-1（以前称为ceNaDC 1）和ceNAC-3（以前称为ceNaDC 2）不同的特征。运输过程是产电的。如在电压钳条件下表达转运蛋白的卵母细胞中底物诱导的内向电流所证明的。利用基因融合技术在转基因C.线虫的研究表明，该基因在肠道中表达，肠道不仅负责消化和吸收营养物质，而且还负责储存能量。通过RNAi（RNA干扰）功能性敲除转运蛋白不仅导致寿命的显着增加，而且还导致体型和脂肪含量的显着降低。ceNAC-2的底物在代谢能量产生以及胆固醇和脂肪酸的生物合成中起关键作用。目前的研究表明，RNAi对这些代谢功能的抑制与寿命的延长以及脂肪含量和体型的减少有关。
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 Xenopas 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.