Indy is a gene in Drosophila melanogaster which, when made dysfunctional, leads to an extension of the average adult life span of the organism. The present study was undertaken to clone the Indy gene-product and to establish its functional identity. We isolated a full-length Indy cDNA from a D. melanogaster cDNA library. The cDNA codes for a protein of 572 amino acids [(Drosophila Indy (drIndy)]. In its amino acid sequence, drIndy exhibits comparable similarity to the two known Na+-coupled dicarboxylate transporters in mammals; namely, NaDC1 (35% identity) and NaDC3 (34% identity). We elucidated the functional characteristics of drIndy in two different heterologous expression systems by using mammalian cells and Xenopus laevis oocytes. These studies show that drIndy is a cation-independent electroneutral transporter for a variety of tricarboxylic acid-cycle intermediates, with preference for citrate compared with succinate. These characteristics of drIndy differ markedly from those of NaDC1 and NaDC3, indicating that neither of these latter transporters is the mammalian functional counterpart of drIndy. Since drIndy is a transporter for tricarboxylic acid-cycle intermediates, dysfunction of the Indy gene may lead to decreased production of metabolic energy in cells, analogous to caloric restriction. This might provide the molecular basis for the observation that disruption of the Indy gene function in Drosophila leads to extension of the average adult life span of the organism.
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Research Article|
October 15 2002
Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates
Katsuhisa INOUE;
Katsuhisa INOUE
∗Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, CB2208, Augusta, GA 30912, U.S.A.,
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You-Jun FEI;
You-Jun FEI
∗Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, CB2208, Augusta, GA 30912, U.S.A.,
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Wei HUANG;
Wei HUANG
∗Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, CB2208, Augusta, GA 30912, U.S.A.,
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Lina ZHUANG;
Lina ZHUANG
∗Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, CB2208, Augusta, GA 30912, U.S.A.,
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Zhong CHEN;
Zhong CHEN
∗Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, CB2208, Augusta, GA 30912, U.S.A.,
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Vadivel GANAPATHY
Vadivel GANAPATHY
1
∗Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, CB2208, Augusta, GA 30912, U.S.A.,
†Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, GA 30912, U.S.A.
1To whom correspondence should be addressed (e-mail vganapat@mail.mcg.edu).
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Publisher: Portland Press Ltd
Received:
July 17 2002
Revision Received:
August 13 2002
Accepted:
August 19 2002
Accepted Manuscript online:
August 19 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 367 (2): 313–319.
Article history
Received:
July 17 2002
Revision Received:
August 13 2002
Accepted:
August 19 2002
Accepted Manuscript online:
August 19 2002
Citation
Katsuhisa INOUE, You-Jun FEI, Wei HUANG, Lina ZHUANG, Zhong CHEN, Vadivel GANAPATHY; Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates. Biochem J 15 October 2002; 367 (2): 313–319. doi: https://doi.org/10.1042/bj20021132
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