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Gene Review

Indy  -  I'm not dead yet

Drosophila melanogaster

Synonyms: BEST:LP01220, CG3979, Dmel\CG3979, INDY, INDY transporter protein, ...
 
 
 

Basic information on Indy

  • A new longevity gene, Indy (for I'm not dead yet), which doubles the average life span of flies without a loss of fertility or physical activity, was postulated to extend life by affecting intermediary metabolism [1].
 

High impact information on Indy

  • Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates [2].
  • Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly [2].
  • Single gene mutations known to extend lifespan in the fly such as Indy and rpd3 also extend lifespan in this assay [3].
  • However, Indy mutants on a decreased-calorie diet have reduced fecundity, suggesting that a tradeoff between longevity and this aspect of performance is conditional, i.e., the tradeoff can occur in a stressful environment while being absent in a more favorable environment [4].
  • These two transporters show significant sequence homology with the product of the Indy gene identified in Drosophila melanogaster and with the Na(+)-coupled dicarboxylate transporters NaDC1 and NaDC3 identified in mammals [5].
  • Only males of the one original Indy line were found to be long-lived. The male-specific lifespan extension seen in this mutant was abolished when the Indy mutation was backcrossed into an outbred genetic background or when treated with tetracycline to cure Wolbachia endosymbiont infection [6]. [7]  
 

Biological context of Indy

  • Our analyses also show that while chico(1) and Indy mutants both exhibit attenuated locomotor declines, the impact of chico loss of function on locomotor senescence is substantially greater [8].
  • We isolated a full-length Indy cDNA from a D. melanogaster cDNA library [9].
  • The effect of decreasing INDY activity, as in the long-lived Indy mutants, may be to alter energy metabolism in a manner that favours lifespan extension [10].
  • 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) [9].
 

Anatomical context of Indy

  • We elucidated the functional characteristics of drIndy in two different heterologous expression systems by using mammalian cells and Xenopus laevis oocytes [9].
 

Associations of Indy with chemical compounds

  • Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action [11].
  • The Indy protein from Drosophila, involved in determining lifespan, and the plant vacuolar malate transporter are both sodium-independent dicarboxylate transporters, possibly acting as exchangers [12].
  • 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 [9].
 

Analytical, diagnostic and therapeutic context of Indy

 

References

  1. Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy. Knauf, F., Rogina, B., Jiang, Z., Aronson, P.S., Helfand, S.L. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Extended life-span conferred by cotransporter gene mutations in Drosophila. Rogina, B., Reenan, R.A., Nilsen, S.P., Helfand, S.L. Science (2000) [Pubmed]
  3. An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster. Bauer, J.H., Goupil, S., Garber, G.B., Helfand, S.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Conditional tradeoffs between aging and organismal performance of Indy long-lived mutant flies. Marden, J.H., Rogina, B., Montooth, K.L., Helfand, S.L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. Structural and functional characteristics of two sodium-coupled dicarboxylate transporters (ceNaDC1 and ceNaDC2) from Caenorhabditis elegans and their relevance to life span. Fei, Y.J., Inoue, K., Ganapathy, V. J. Biol. Chem. (2003) [Pubmed]
  6. No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects. Toivonen, J.M., Walker, G.A., Martinez-Diaz, P., Bjedov, I., Driege, Y., Jacobs, H.T., Gems, D., Partridge, L. PLoS. Genet. (2007) [Pubmed]
  7. Longevity of Indy mutant Drosophila not attributable to Indy mutation. Toivonen, J.M., Gems, D., Partridge, L. Proc. Natl. Acad. Sci. U. S. A. (2009) [Pubmed]
  8. Distinct genetic influences on locomotor senescence in Drosophila revealed by a series of metrical analyses. Martin, I., Grotewiel, M.S. Exp. Gerontol. (2006) [Pubmed]
  9. Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates. Inoue, K., Fei, Y.J., Huang, W., Zhuang, L., Chen, Z., Ganapathy, V. Biochem. J. (2002) [Pubmed]
  10. The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates. Knauf, F., Mohebbi, N., Teichert, C., Herold, D., Rogina, B., Helfand, S., Gollasch, M., Luft, F.C., Aronson, P.S. Biochem. J. (2006) [Pubmed]
  11. Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. Inoue, K., Zhuang, L., Maddox, D.M., Smith, S.B., Ganapathy, V. Biochem. J. (2003) [Pubmed]
  12. Molecular properties of the SLC13 family of dicarboxylate and sulfate transporters. Pajor, A.M. Pflugers Arch. (2006) [Pubmed]
  13. Functional features and genomic organization of mouse NaCT, a sodium-coupled transporter for tricarboxylic acid cycle intermediates. Inoue, K., Fei, Y.J., Zhuang, L., Gopal, E., Miyauchi, S., Ganapathy, V. Biochem. J. (2004) [Pubmed]
 
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