The mitochondrial pyruvate carrier in health and disease: To carry or not to carry?

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1863, Issue 10, 2016, Pages 2436-2442

  Bender, Tom ^a   Martinou, Jean Claude ^a  

^a UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

Gluconeogenesis; Metabolism; Mitochondria; Mitochondrial pyruvate carrier; Warburg effect

Indexed keywords

MITOCHONDRIAL PYRUVATE CARRIER; MONOCARBOXYLATE TRANSPORTER; UNCLASSIFIED DRUG; ANION TRANSPORT PROTEIN; CARRIER PROTEIN; DROSOPHILA PROTEIN; GLUCOSE; MITOCHONDRIAL PROTEIN; MPC1 PROTEIN, HUMAN; PYRUVIC ACID; SACCHAROMYCES CEREVISIAE PROTEIN;

CANCER CELL; CANCER GROWTH; ENERGY METABOLISM; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLYCOLYSIS; HUMAN; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; REVIEW; ANIMAL; DEFICIENCY; GENETICS; HOMEOSTASIS; LIVER; MAMMAL; METABOLISM; MITOCHONDRIAL MEMBRANE; NEOPLASM; OXIDATIVE PHOSPHORYLATION;

ANIMALS; ANION TRANSPORT PROTEINS; DIABETES MELLITUS, TYPE 2; DROSOPHILA PROTEINS; ENERGY METABOLISM; GLUCOSE; HOMEOSTASIS; HUMANS; LIVER; MAMMALS; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIAL MEMBRANES; MITOCHONDRIAL PROTEINS; NEOPLASMS; OXIDATIVE PHOSPHORYLATION; PYRUVIC ACID; SACCHAROMYCES CEREVISIAE PROTEINS;

EID: 84957675933     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2016.01.017     Document Type: Review

References (62)

1. Kunji, E.R., Robinson, A.J., Coupling of proton and substrate translocation in the transport cycle of mitochondrial carriers. Curr. Opin. Struct. Biol. 20 (2010), 440–447.
2. Palmieri, F., The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol. Asp. Med. 34 (2013), 465–484.
3. Bricker, D.K., Taylor, E.B., Schell, J.C., Orsak, T., Boutron, A., Chen, Y.C., Cox, J.E., Cardon, C.M., Van Vranken, J.G., Dephoure, N., Redin, C., Boudina, S., Gygi, S.P., Brivet, M., Thummel, C.S., Rutter, J., A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science 337 (2012), 96–100.
4. Herzig, S., Raemy, E., Montessuit, S., Veuthey, J.L., Zamboni, N., Westermann, B., Kunji, E.R., Martinou, J.C., Identification and functional expression of the mitochondrial pyruvate carrier. Science 337 (2012), 93–96.
5. Gray, L.R., Tompkins, S.C., Taylor, E.B., Regulation of pyruvate metabolism and human disease. Cell. Mol. Life Sci. 74 (2013), 2577–2604.
6. Halestrap, A.P., Denton, R.M., Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate. Biochem. J. 138 (1974), 313–316.
7. Papa, S., Francavilla, A., Paradies, G., Meduri, B., The transport of pyruvate in rat liver mitochondria. FEBS Lett. 12 (1971), 285–288.
8. Halestrap, A.P., The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem. J. 148 (1975), 85–96.
9. Schell, J.C., Rutter, J., The long and winding road to the mitochondrial pyruvate carrier. Cancer Metab., 1, 2013, 6.
10. Vanderperre, B., Bender, T., Kunji, E.R.S., Martinou, J.C., Mitochondrial pyruvate import and its effects on homeostasis. Curr. Opin. Cell Biol. 33 (2015), 35–41.
11. Kohlhaw, G.B., Leucine biosynthesis in fungi: entering metabolism through the back door. Microbiol. Mol. Biol. Rev. 67 (2003), 1–15.
12. Colca, J.R., McDonald, W.G., Cavey, G.S., Cole, S.L., Holewa, D.D., Brightwell-Conrad, A.S., Wolfe, C.L., Wheeler, J.S., Coulter, K.R., Kilkuskie, P.M., Gracheva, E., Korshunova, Y., Trusgnich, M., Karr, R., Wiley, S.E., Divakaruni, A.S., Murphy, A.N., Vigueira, P.A., Finck, B.N., Kletzien, R.F., Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT)—relationship to newly identified mitochondrial pyruvate carrier proteins. PLoS One, 8, 2013, e61551.
13. Divakaruni, A.S., Wiley, S.E., Rogers, G.W., Andreyev, A.Y., Petrosyan, S., Loviscach, M., Wall, E.A., Yadava, N., Heuck, A.P., Ferrick, D.A., Henry, R.R., McDonald, W.G., Colca, J.R., Simon, M.I., Ciaraldi, T.P., Murphy, A.N., Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 5422–5427.
14. Du, J., Cleghorn, W.M., Contreras, L., Lindsay, K., Rountree, A.M., Chertov, A.O., Turner, S.J., Sahaboglu, A., Linton, J., Sadilek, M., Satrustegui, J., Sweet, I.R., Paquet-Durand, F., Hurley, J.B., Inhibition of mitochondrial pyruvate transport by zaprinast causes massive accumulation of aspartate at the expense of glutamate in the retina. J. Biol. Chem. 288 (2013), 36129–36140.
15. Compan, V., Pierredon, S., Vanderperre, B., Krznar, P., Marchiq, I., Zamboni, N., Pouyssegur, J., Martinou, J.C., Monitoring mitochondrial pyruvate carrier activity in real time using a BRET-Based Biosensor: investigation of the Warburg effect. Mol. Cell 59 (2015), 491–501.
16. Bender, T., Pena, G., Martinou, J.C., Regulation of mitochondrial pyruvate uptake by alternative pyruvate carrier complexes. EMBO J. 34 (2015), 911–924.
17. Schell, J.C., Olson, K.A., Jiang, L., Hawkins, A.J., Van Vranken, J.G., Xie, J., Egnatchik, R.A., Earl, E.G., DeBerardinis, R.J., Rutter, J., A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and Colon Cancer Cell growth. Mol. Cell 56 (2014), 400–413.
18. Vacanti, N.M., Divakaruni, A.S., Green, C.R., Parker, S.J., Henry, R.R., Ciaraldi, T.P., Murphy, A.N., Metallo, C.M., Regulation of substrate utilization by the mitochondrial pyruvate carrier. Mol. Cell 56 (2014), 425–435.
19. McCommis, K.S., Chen, Z., Fu, X., McDonald, W.G., Colca, J.R., Kletzien, R.F., Burgess, S.C., Finck, B.N., Loss of mitochondrial pyruvate carrier 2 in the liver leads to defects in gluconeogenesis and compensation via pyruvate-alanine cycling. Cell Metab. 22 (2015), 682–694.
20. Gray, L.R., Sultana, M.R., Rauckhorst, A.J., Oonthonpan, L., Tompkins, S.C., Sharma, A., Fu, X., Miao, R., Pewa, A.D., Brown, K.S., Lane, E.E., Dohlman, A., Zepeda-Orozco, D., Xie, J., Rutter, J., Norris, A.W., Cox, J.E., Burgess, S.C., Potthoff, M.J., Taylor, E.B., Hepatic mitochondrial pyruvate carrier 1 Is required for efficient regulation of gluconeogenesis and whole-body glucose homeostasis. Cell Metab. 22 (2015), 669–681.
21. Xu, Y., Tao, Y., Cheung, L.S., Fan, C., Chen, L.Q., Xu, S., Perry, K., Frommer, W.B., Feng, L., Structures of bacterial homologues of SWEET transporters in two distinct conformations. Nature 515 (2014), 448–452.
22. Brivet, M., Garcia-Cazorla, A., Lyonnet, S., Dumez, Y., Nassogne, M.C., Slama, A., Boutron, A., Touati, G., Legrand, A., Saudubray, J.M., Impaired mitochondrial pyruvate importation in a patient and a fetus at risk. Mol. Genet. Metab. 78 (2003), 186–192.
23. Vigueira, P.A., McCommis, K.S., Schweitzer, G.G., Remedi, M.S., Chambers, K.T., Fu, X., McDonald, W.G., Cole, S.L., Colca, J.R., Kletzien, R.F., Burgess, S.C., Finck, B.N., Mitochondrial pyruvate carrier 2 hypomorphism in mice leads to defects in glucose-stimulated insulin secretion. Cell Rep. 7 (2014), 2042–2053.
24. Yang, C., Ko, B., Hensley, C.T., Jiang, L., Wasti, A.T., Kim, J., Sudderth, J., Calvaruso, M.A., Lumata, L., Mitsche, M., Rutter, J., Merritt, M.E., DeBerardinis, R.J., Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol. Cell 56 (2014), 414–424.
25. Timón-Gómez, A., Proft, M., Pascual-Ahuir, A., Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast. PLoS One, 8, 2013, e79405.
26. Boubekeur, S., Bunoust, O., Camougrand, N., Castroviejo, M., Rigoulet, M., Guérin, B., A mitochondrial pyruvate dehydrogenase bypass in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 274 (1999), 21044–21048.
27. Vander Heiden, M.G., Cantley, L.C., Thompson, C.B., Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324 (2009), 1029–1033.
28. Koppenol, W.H., Bounds, P.L., Dang, C.V., Otto Warburg's contributions to current concepts of cancer metabolism. Nat. Rev. Cancer 11 (2011), 325–337.
29. Cairns, R.A., Harris, I.S., Mak, T.W., Regulation of cancer cell metabolism. Nat. Rev. Cancer 11 (2011), 85–95.
30. Kim, J.W., Tchernyshyov, I., Semenza, G.L., Dang, C.V., HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3 (2006), 177–185.
31. Papandreou, I., Cairns, R.A., Fontana, L., Lim, A.L., Denko, N.C., HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 3 (2006), 187–197.
32. Le, A., Cooper, C.R., Gouw, A.M., Dinavahi, R., Maitra, A., Deck, L.M., Royer, R.E., Vander Jagt, D.L., Semenza, G.L., Dang, C.V., Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 2037–2042.
33. Michelakis, E.D., Sutendra, G., Dromparis, P., Webster, L., Haromy, A., Niven, E., Maguire, C., Gammer, T.L., Mackey, J.R., Fulton, D., Abdulkarim, B., McMurtry, M.S., Petruk, K.C., Metabolic modulation of glioblastoma with dichloroacetate. Sci. Transl. Med., 2, 2010 (31ra34).
34. Xie, H., Hanai, J., Ren, J.G., Kats, L., Burgess, K., Bhargava, P., Signoretti, S., Billiard, J., Duffy, K.J., Grant, A., Wang, X., Lorkiewicz, P.K., Schatzman, S., Bousamra, M. 2nd, Lane, A.N., Higashi, R.M., Fan, T.W., Pandolfi, P.P., Sukhatme, V.P., Seth, P., Targeting lactate dehydrogenase—a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells. Cell Metab. 19 (2014), 795–809.
35. Deng, W.J., Nie, S., Dai, J., Wu, J.R., Zeng, R., Proteome, phosphoproteome, and hydroxyproteome of liver mitochondria in diabetic rats at early pathogenic stages. Mol. Cell. Proteomics 9 (2010), 100–116.
36. Hebert, A.S., Dittenhafer-Reed, K.E., Yu, W., Bailey, D.J., Selen, E.S., Boersma, M.D., Carson, J.J., Tonelli, M., Balloon, A.J., Higbee, A.J., Westphall, M.S., Pagliarini, D.J., Prolla, T.A., Assadi-Porter, F., Roy, S., Denu, J.M., Coon, J.J., Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol. Cell 49 (2013), 186–199.
37. Liang, L., Li, Q., Huang, L., Li, D., Li, X., Sirt3 binds to and deacetylates mitochondrial pyruvate carrier 1 to enhance its activity. Biochem. Biophys. Res. Commun., 2015.
38. Sack, M.N., Finkel, T., Mitochondrial metabolism, sirtuins, and aging. Cold Spring Harb. Perspect. Biol., 4, 2012, a013102.
39. Schmidt, O., Harbauer, A.B., Rao, S., Eyrich, B., Zahedi, R.P., Stojanovski, D., Schonfisch, B., Guiard, B., Sickmann, A., Pfanner, N., Meisinger, C., Regulation of mitochondrial protein import by cytosolic kinases. Cell 144 (2011), 227–239.
40. Diaz-Ruiz, R., Rigoulet, M., Devin, A., The Warburg and Crabtree effects: on the origin of cancer cell energy metabolism and of yeast glucose repression. Biochim. Biophys. Acta 1807 (2011), 568–576.
41. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144 (2011), 646–674.
42. Ito, K., Suda, T., Metabolic requirements for the maintenance of self-renewing stem cells. Nat. Rev. Mol. Cell. Biol. 15 (2014), 243–256.
43. Zhong, Y., Li, X., Yu, D., Li, X., Li, Y., Long, Y., Yuan, Y., Ji, Z., Zhang, M., Wen, J.G., Nesland, J.M., Suo, Z., Application of Mitochondrial Pyruvate Carrier Blocker UK5099 Creates Metabolic Reprogram and Greater Stem-Like Properties in LnCap Prostate Cancer Cells in Vitro, Oncotarget. 2015.
44. Christofk, H.R., Vander Heiden, M.G., Harris, M.H., Ramanathan, A., Gerszten, R.E., Wei, R., Fleming, M.D., Schreiber, S.L., Cantley, L.C., The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452 (2008), 230–233.
45. Le Floch, R., Chiche, J., Marchiq, I., Naiken, T., Ilc, K., Murray, C.M., Critchlow, S.E., Roux, D., Simon, M.P., Pouyssegur, J., CD147 subunit of lactate/H + symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 16663–16668.
46. Garon, E.B., Christofk, H.R., Hosmer, W., Britten, C.D., Bahng, A., Crabtree, M.J., Hong, C.S., Kamranpour, N., Pitts, S., Kabbinavar, F., Patel, C., von Euw, E., Black, A., Michelakis, E.D., Dubinett, S.M., Slamon, D.J., Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer. J. Cancer Res. Clin. Oncol. 140 (2014), 443–452.
47. Wise, D.R., Thompson, C.B., Glutamine addiction: a new therapeutic target in cancer. Trends Biochem. Sci. 35 (2010), 427–433.
48. Burgess, S.C., Leone, T.C., Wende, A.R., Croce, M.A., Chen, Z., Sherry, A.D., Malloy, C.R., Finck, B.N., Diminished hepatic gluconeogenesis via defects in tricarboxylic acid cycle flux in peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)-deficient mice. J. Biol. Chem. 281 (2006), 19000–19008.
49. Satapati, S., Sunny, N.E., Kucejova, B., Fu, X., He, T.T., Mendez-Lucas, A., Shelton, J.M., Perales, J.C., Browning, J.D., Burgess, S.C., Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver. J. Lipid Res. 53 (2012), 1080–1092.
50. Martin-Requero, A., Ayuso, M.S., Parrilla, R., Rate-limiting steps for hepatic gluconeogenesis. Mechanism of oxamate inhibition of mitochondrial pyruvate metabolism. J. Biol. Chem. 261 (1986), 13973–13978.
51. Rognstad, R., The role of mitochondrial pyruvate transport in the control of lactate gluconeogenesis. Int. J. Biochem. 15 (1983), 1417–1421.
52. Thomas, A.P., Halestrap, A.P., The role of mitochondrial pyruvate transport in the stimulation by glucagon and phenylephrine of gluconeogenesis from L-lactate in isolated rat hepatocytes. Biochem. J. 198 (1981), 551–560.
53. Sugden, M.C., Holness, M.J., The pyruvate carboxylase-pyruvate dehydrogenase axis in islet pyruvate metabolism: going round in circles?. Islets 3 (2011), 302–319.
54. Jensen, M.V., Joseph, J.W., Ronnebaum, S.M., Burgess, S.C., Sherry, A.D., Newgard, C.B., Metabolic cycling in control of glucose-stimulated insulin secretion. Am. J. Physiol. Endocrinol. Metab. 295 (2008), E1287–E1297.
55. Patterson, J.N., Cousteils, K., Lou, J.W., Manning Fox, J.E., MacDonald, P.E., Joseph, J.W., Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated insulin secretion. J. Biol. Chem. 289 (2014), 13335–13346.
56. San Martin, A., Ceballo, S., Baeza-Lehnert, F., Lerchundi, R., Valdebenito, R., Contreras-Baeza, Y., Alegria, K., Barros, L.F., Imaging mitochondrial flux in single cells with a FRET sensor for pyruvate. PLoS One, 9, 2014, e85780.
57. Zamboni, N., Saghatelian, A., Patti, G.J., Defining the metabolome: size, flux, and regulation. Mol. Cell 58 (2015), 699–706.
58. Cybulski, R.L., Fisher, R.R., Mitochondrial neutral amino acid transport: evidence for a carrier mediated mechanism. Biochemistry 16 (1977), 5116–5120.
59. Dieterle, P., Brawand, F., Moser, U.K., Walter, P., Alanine metabolism in rat liver mitochondria. Eur. J. Biochem. 88 (1978), 467–473.
60. Indiveri, C., Abruzzo, G., Stipani, I., Palmieri, F., Identification and purification of the reconstitutively active glutamine carrier from rat kidney mitochondria. Biochem. J. 333 (1998), 285–290.
61. Pagliarini, D.J., Rutter, J., Hallmarks of a new era in mitochondrial biochemistry. Genes Dev. 27 (2013), 2615–2627.
62. Schmidt, O., Pfanner, N., Meisinger, C., Mitochondrial protein import: from proteomics to functional mechanisms. Nat. Rev. Mol. Cell. Biol. 11 (2010), 655–667.