Mitochondrial and plasma membrane citrate transporters: Discovery of selective inhibitors and application to structure/function analysis

Molecular and Cellular Pharmacology

Volumn 2, Issue 3, 2010, Pages 101-110

  Sun, Jiakang ^a   Aluvila, Sreevidya ^a   Kotaria, Rusudan ^a   Mayor, June A ^a   Walters, D Eric ^a   Kaplan, Ronald S ^a  

^a ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE   (United States)

Author keywords

Bioenergetics; Citrate; Inhibitor discovery; Mitochondria; Plasma membrane; Transporter

Indexed keywords

AMINO ACID TRANSPORTER; CARRIER PROTEIN; CITRIC ACID TRANSPORTER; CITRIC ACID TRANSPORTER INHIBITOR; LEUCINE TRANSPORTER; PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; BIOENERGY; CELL MEMBRANE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; MITOCHONDRIAL MEMBRANE; MOLECULAR MECHANICS; PROTEIN INTERACTION; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION;

EID: 77954273723     PISSN: None     EISSN: 19381247     Source Type: Journal    
DOI: 10.4255/mcpharmacol.10.14     Document Type: Article

References (42)

1. Kaplan RS, Mayor JA. Structure, function and regulation of the tricarboxylate transport protein from rat liver mitochondria. J Bioenerg Biomembr 1993;25:503-514.
2. Spencer AF, Lowenstein JM. The supply of precursors for the synthesis of fatty acids. J Biol Chem 1962;237:3640-3648.
3. Srere PA, Bhaduri A. Incorporation of radioactive citrate into fatty acids. Biochim Biophys Acta 1962;59:487-489.
4. Watson JA, Lowenstein JM. Citrate and the conversion of carbohydrate into fat. Fatty acid synthesis by a combination of cytoplasm and mitochondria. J Biol Chem 1970;245:5993-6002.
5. Greville GD. Intracellular compartmentation and the citric acid cycle. In: Lowenstein JM, editor. Citric acid cycle control and compartmentation. New York: Marcel Dekker; 1969. p. 1-136.
6. Inoue K, Zhuang L, Maddox DM, et al. Structure, function, and expression pattern of a novel sodium- coupled citrate transporter (NaCT) cloned from mammalian brain. J Biol Chem 2007;277:39469-39476.
7. Gopal E, Miyauchi S, Martin PM, et al. Expression and functional features of NaCT, a sodium-coupled citrate transporter, in human and rat livers and cell lines. Am J Physiol Gastrointest Liver Physiol 2007;292:G402-G408.
8. Rogina B, Reenan RA, Nilsen SP, et al. Extended lifespan conferred by cotransporter gene mutations in Drosophila. Science 2000;290:2137-2140.
9. Inoue K, Fei YJ, Huang W, et al. Functional identity of Drosophila melanogaster indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates. Biochem J 2002;367:313-319.
10. Inoue K, Zhuang L, Ganapathy V. Human Na+- coupled citrate transporter: primary structure, genomic organization, and transport function. Biochem Biophys Res Commun 2002;299:465-471.
11. Inoue K, Fei YJ, Zhuang L, et al. Functional features and genomic organization of mouse NaCT, a sodium-coupled transporter for tricarboxylic acid cycle intermediates. Biochem J 2004;378:949-957.
12. Fei YJ, Liu JC, Inoue K, et al. Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size and fat content in Caenorhabditis elegans. Biochem J 2004;379:191-198.
13. Knauf F, Mohebbi N, Teichert C, et al. The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates. Biochem J 2006;397:25-29.
14. Robinson BH, Williams GR, Halperin ML, et al. Factors affecting the kinetics and equilibrium of exchange reactions of the citrate-transporting system of rat liver mitochondria. J Biol Chem 1971;246:5280-5286.
15. Robinson BH, Williams GR, Halperin ML, et al. The sensitivity of the exchange reactions of tricarboxylate, 2-oxoglutarate and dicarboxylate transporting systems of rat liver mitochondria to inhibition by 2-pentylmalonate, p-iodobenzylmalonate, and benzene 1,2,3-tricarboxylate. Eur J Biochem 1971;20:65-71.
16. Palmieri F, Stipani I, Quagliariello E, et al. Kinetic study of the tricarboxylate carrier in rat liver mitochondria. Eur J Biochem 1972;26:587-594.
17. Kaplan RS, Mayor JA, Gremse DA, et al. High level expression and characterization of the mitochondrial citrate transport protein from the yeast Saccharomyces cerevisiae. J Biol Chem 1995;270:4108-4114.
18. Xu Y, Kakhniashvili DA, Gremse DA, et al. The yeast mitochondrial citrate transport protein: probing the roles of cysteines, Argl81, and Argl89 in transporter function. J Biol Chem 2000;275:7117-7124.
19. Kaplan RS. Structure and function of mitochondrial anion transport proteins. J Membrane Biol 2001;179:165-183.
20. Kotaria R, Mayor JA, Walters DE, et al. Oligomeric state of wild-type and cysteine-less yeast mitochondrial citrate transport proteins. J Bioenerg Biomemb 1999;31:543-549.
21. Bamber L, Slotboom DJ, Kunji ERS. Yeast mitochondrial ADP/ATP carriers are monomeric in detergents as demonstrated by differential affinity purification. J Mol Biol 2007;371:388-395.
22. Bamber L, Harding M, Monne M, et al. The yeast mitochondrial ADP/ATP carrier functions as a monomer in mitochondrial membranes. Proc Natl Acad Sci USA 2007;104:10830-10834.
23. Lin SJ, Kaeberlein M, Andalis AA, et al. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 2002;418:344-348.
24. Koubova J, Guarente L. How does calorie restriction work? Genes Dev 2003;17:313-321.
25. Masoro EJ. Caloric restriction and aging: an update. Exp Gerontol 2000;35:299-305.
26. Wang PY, Neretti N, Whitaker R, et al. Long-lived indy and calorie restriction interact to extend life span. Proc Natl Acad Sci U S A 2009;106:9262-9267.
27. Neretti N, Wang PY, Brodsky AS, et al. Long-lived indy induces reduced mitochondrial reactive oxygen species production and oxidative damage. Proc Natl Acad Sci U S A 2009;106:2277-2282.
28. Knauf F, Rogina B, Jiang Z, Aronson PS, Helfand SL. Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy. Proc. Natl Acad Sci USA 2002;99:14315-14319.
29. Aluvila S, Sun J, Harrison DHT, et al. Inhibitors of the mitochondrial citrate transport protein: Validation of the role of substrate binding residues and discovery of the first purely competitive inhibitor. Mol Pharmacol 2010;77:26-34.
30. Irwin JJ, Shoichet BK. ZINC - a free database of commercially available compounds for virtual screening. J Chem Inf Model 2005;45:177-182.
31. Xu Y, Mayor JA, Gremse D, et al. High-yield bacterial expression, purification, and functional reconstitution of the tricarboxylate transport protein from rat liver mitochondria. Biochem Biophys Res Commun 1995;207:783-789.
32. Ma C, Remani S, Sun J, et al. Identification of the substrate binding sites within the yeast mitochondrial citrate transport protein. J Biol Chem 2007;282:17210-17220.
33. Kaplan RS, Mayor JA, Johnston N, et al. Purification and characterization of the reconstitutively active tricarboxylate transporter from rat liver mitochondria. J Biol Chem 1990;265:13379-13385.
34. Kaplan RS, Pedersen PL. Determination of microgram quantities of protein in the presence of milligram levels of lipid with amido black 10B. Anal Biochem 1985; 150:97-104.
35. Snider C, Jayasinghe S, Hristova K, et al. MPEx: a tool for exploring membrane proteins. Protein Sci 2009;18:2624-1628.
36. Hessa T, Meindl-Beinker NM, Bernsel A, et al. Molecular code for transmembrane-helix recognition by the Sec61 translocon. Nature 2007;450:1026-1030.
37. Singh SK, Yamashita A, Gouaux E. Antidepressant binding site in a bacterial homologue of neurotransmitter transporters. Nature 2007;448:952-956.
38. Walters DE, Kaplan RS. Homology-modeled structure of the yeast mitochondrial citrate transport protein. Biophys J 2004;87:907-911.
39. Merluzzi VJ, Hargrave KD, Labadia M, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science 1990;250:1411-1413.
40. Dooley M, Lamb HM. Donepezil: a review of its use in Alzheimer's disease. Drugs Aging 2000;16:199-226.
41. Prusakiewicz JJ, Duggan KC, Rouzer CA, et al. Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2- arachidonoylglycerol by ibuprofen and mefenamic acid. Biochemistry 2009;48:7353-7355.
42. Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, et al. Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature 2003;426:39-44.