Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates.
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.
Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, CB2208, Augusta, GA 30912, U.S.A.
Katsuhisa
K
Inoue
You-Jun
YJ
Fei
Wei
W
Huang
Lina
L
Zhuang
Zhong
Z
Chen
Vadivel
V
Ganapathy
D000818:Animals; D002412:Cations / Q000378:metabolism; D002478:Cells, Cultured; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle / Q000502:physiology; D003001:Cloning, Molecular; D029382:Dicarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019289:Pyruvic Acid / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013379:Substrate Specificity; D019802:Succinic Acid / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D002412:Cations; D029382:Dicarboxylic Acid Transporters; D029721:Drosophila Proteins; C417606:Indy protein, Drosophila; D027981:Symporters; D019343:Citric Acid; D019289:Pyruvic Acid; D012964:Sodium; D019802:Succinic Acid