UCP2, not a physiologically relevant uncoupler but a glucose sparing switch impacting ROS production and glucose sensing

Biochimica et Biophysica Acta - Bioenergetics

Volumn 1787, Issue 5, 2009, Pages 377-383

  Bouillaud, Frédéric ^a  

^a UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

Diabetes; Glutamine; Glycolysis; Ischemia; Mitochondria

Indexed keywords

GLUCOSE; REACTIVE OXYGEN METABOLITE; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3;

AEROBIC METABOLISM; CELL METABOLISM; GLYCOLYSIS; ISCHEMIA; MITOCHONDRIAL RESPIRATION; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TRANSPORT; REVIEW;

ADENOSINE TRIPHOSPHATE; ADIPOSE TISSUE; ADIPOSE TISSUE, BROWN; AEROBIOSIS; ANIMALS; GLUCOSE; GLYCOLYSIS; HUMANS; ION CHANNELS; MAMMALS; MITOCHONDRIAL PROTEINS; OXYGEN CONSUMPTION; REACTIVE OXYGEN SPECIES; YEASTS;

MAMMALIA;

EID: 65549105815     PISSN: 00052728     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbabio.2009.01.003     Document Type: Review

References (58)

1. Arsenijevic D., Onuma H., Pecqueur C., Raimbault S., Manning B.S., Miroux B., Couplan E., Alves-Guerra M.C., Goubern M., Surwit R., Bouillaud F., Richard D., Collins S., and Ricquier D. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat. Genet. 26 (2000) 435-439
2. Zhang C.Y., Baffy G., Perret P., Krauss S., Peroni O., Grujic D., Hagen T., Vidal-Puig A.J., Boss O., Kim Y.B., Zheng X.X., Wheeler M.B., Shulman G.I., Chan C.B., and Lowell B.B. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105 (2001) 745-755
3. Parton L.E., Ye C.P., Coppari R., Enriori P.J., Choi B., Zhang C.Y., Xu C., Vianna C.R., Balthasar N., Lee C.E., Elmquist J.K., Cowley M.A., and Lowell B.B. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449 (2007) 228-232
4. Blanc J., Alves-Guerra M.C., Esposito B., Rousset S., Gourdy P., Ricquier D., Tedgui A., Miroux B., and Mallat Z. Protective role of uncoupling protein 2 in atherosclerosis. Circulation 107 (2003) 388-390
5. Mattiasson G., Shamloo M., Gido G., Mathi K., Tomasevic G., Yi S., Warden C.H., Castilho R.F., Melcher T., Gonzalez-Zulueta M., Nikolich K., and Wieloch T. Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat. Med. 9 (2003) 1062-1068
6. Bouillaud F., Ricquier D., Thibault J., and Weissenbach J. Molecular approach to thermogenesis in brown adipose tissue: cDNA cloning of the mitochondrial uncoupling protein. Proc. Natl. Acad. Sci. U. S. A. 82 (1985) 445-448
7. Ricquier D., and Bouillaud F. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem. J. 345 Pt. 2 (2000) 161-179
8. Gonzalez-Barroso M.M., Fleury C., Bouillaud F., Nicholls D.G., and Rial E. The uncoupling protein UCP1 does not increase the proton conductance of the inner mitochondrial membrane by functioning as a fatty acid anion transporter. J. Biol. Chem. 273 (1998) 15528-15532
9. Garlid K.D., Orosz D.E., Modriansky M., Vassanelli S., and Jezek P. On the mechanism of fatty acid-induced proton transport by mitochondrial uncoupling protein. J. Biol. Chem. 271 (1996) 2615-2620
10. Rial E., Gonzalez-Barroso M., Fleury C., Iturrizaga S., Sanchis D., Jimenez-Jimenez J., Ricquier D., Goubern M., and Bouillaud F. Retinoids activate proton transport by the uncoupling proteins UCP1 and UCP2. EMBO J. 18 (1999) 5827-5833
11. Echtay K.S., Winkler E., Frischmuth K., and Klingenberg M. Uncoupling proteins 2 and 3 are highly active H(+) transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone). Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 1416-1421
12. Echtay K.S., Esteves T.C., Pakay J.L., Jekabsons M.B., Lambert A.J., Portero-Otin M., Pamplona R., Vidal-Puig A.J., Wang S., Roebuck S.J., and Brand M.D. A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling. EMBO J. 22 (2003) 4103-4110
13. Jaburek M., and Garlid K.D. Reconstitution of recombinant uncoupling proteins: UCP1, -2, and -3 have similar affinities for ATP and are unaffected by coenzyme Q10. J. Biol. Chem. 278 (2003) 25825-25831
14. Criscuolo F., Gonzalez-Barroso Mdel M., Le Maho Y., Ricquier D., and Bouillaud F. Avian uncoupling protein expressed in yeast mitochondria prevents endogenous free radical damage. Proc. Biol. Sci. 272 (2005) 803-810
15. Talbot D.A., Duchamp C., Rey B., Hanuise N., Rouanet J.L., Sibille B., and Brand M.D. Uncoupling protein and ATP/ADP carrier increase mitochondrial proton conductance after cold adaptation of king penguins. J. Physiol. 558 (2004) 123-135
16. Amerkhanov Z.G., Smirnova N.P., Markova O.V., Kolaeva S.G., and Solomonov N.G. Involvement of some carrier proteins in thermoregulatory enhancement of respiration of mitochondria of the liver and skeletal muscles of ground squirrels (Citellus undulatus) awakening from hibernation. Dokl. Biochem. Biophys. 397 (2004) 213-216
17. Criscuolo F., Mozo J., Hurtaud C., Nubel T., and Bouillaud F. UCP2, UCP3, avUCP, what do they do when proton transport is not stimulated? Possible relevance to pyruvate and glutamine metabolism. Biochim. Biophys. Acta 1757 (2006) 1284-1291
18. Parker N., Vidal-Puig A., and Brand M.D. Stimulation of mitochondrial proton conductance by hydroxynonenal requires a high membrane potential. Biosci. Rep. 28 (2008) 83-88
19. Shabalina I.G., Kramarova T.V., Nedergaard J., and Cannon B. Carboxyatractyloside effects on brown-fat mitochondria imply that the adenine nucleotide translocator isoforms ANT1 and ANT2 may be responsible for basal and fatty-acid-induced uncoupling respectively. Biochem. J. 399 (2006) 405-414
20. Nicholls D.G. The physiological regulation of uncoupling proteins. Biochim. Biophys. Acta 1757 (2006) 459-466
21. Andreyev A., Bondareva T.O., Dedukhova V.I., Mokhova E.N., Skulachev V.P., Tsofina L.M., Volkov N.I., and Vygodina T.V. The ATP/ADP-antiporter is involved in the uncoupling effect of fatty acids on mitochondria. Eur. J. Biochem. 182 (1989) 585-592
22. Nicholls D.G., and Lindberg O. Brown-adipose-tissue mitochondria. The influence of albumin and nucleotides on passive ion permeabilities. Eur. J. Biochem. 37 (1973) 523-530
23. Shabalina I.G., Jacobsson A., Cannon B., and Nedergaard J. Native UCP1 displays simple competitive kinetics between the regulators purine nucleotides and fatty acids. J. Biol. Chem. 279 (2004) 38236-38248
24. Trenker M., Malli R., Fertschai I., Levak-Frank S., and Graier W.F. Uncoupling proteins 2 and 3 are fundamental for mitochondrial Ca2+ uniport. Nat. Cell Biol. 9 (2007) 445-452
25. Fleury C., Neverova M., Collins S., Raimbault S., Champigny O., Levi-Meyrueis C., Bouillaud F., Seldin M.F., Surwit R.S., Ricquier D., and Warden C.H. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat. Genet. 15 (1997) 269-272
26. Couplan E., del Mar Gonzalez-Barroso M., Alves-Guerra M.C., Ricquier D., Goubern M., and Bouillaud F. No evidence for a basal, retinoic, or superoxide-induced uncoupling activity of the uncoupling protein 2 present in spleen or lung mitochondria. J. Biol. Chem. 277 (2002) 26268-26275
27. Mozo J., Ferry G., Studeny A., Pecqueur C., Rodriguez M., Boutin J.A., and Bouillaud F. Expression of UCP3 in CHO cells does not cause uncoupling, but controls mitochondrial activity in the presence of glucose. Biochem. J. 393 (2006) 431-439
28. Pecqueur C., Bui T., Gelly C., Hauchard J., Barbot C., Bouillaud F., Ricquier D., Miroux B., and Thompson C.B. Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization. FASEB J. 22 (2007) 9-18
29. Nubel T., Emre Y., Rabier D., Chadefaux B., Ricquier D., and Bouillaud F. Modified glutamine catabolism in macrophages of Ucp2 knock-out mice. Biochim. Biophys. Acta 1777 (2008) 48-54
30. Millet L., Vidal H., Andreelli F., Larrouy D., Riou J.P., Ricquier D., Laville M., and Langin D. Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans. J. Clin. Invest. 100 (1997) 2665-2670
31. Schrauwen P., Hoppeler H., Billeter R., Bakker A.H., and Pendergast D.R. Fiber type dependent upregulation of human skeletal muscle UCP2 and UCP3 mRNA expression by high-fat diet. Int. J. Obes. Relat. Metab. Disord. 25 (2001) 449-456
32. Hurtaud C., Gelly C., Chen Z., Levi-Meyrueis C., and Bouillaud F. Glutamine stimulates translation of uncoupling protein 2mRNA. Cell. Mol. Life Sci. 64 (2007) 1853-1860
33. DeBerardinis R.J., Mancuso A., Daikhin E., Nissim I., Yudkoff M., Wehrli S., and Thompson C.B. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 19345-19350
34. MacLellan J.D., Gerrits M.F., Gowing A., Smith P.J., Wheeler M.B., and Harper M.E. Physiological increases in uncoupling protein 3 augment fatty acid oxidation and decrease reactive oxygen species production without uncoupling respiration in muscle cells. Diabetes 54 (2005) 2343-2350
35. Cadenas S., Buckingham J.A., Samec S., Seydoux J., Din N., Dulloo A.G., and Brand M.D. UCP2 and UCP3 rise in starved rat skeletal muscle but mitochondrial proton conductance is unchanged. FEBS Lett. 462 (1999) 257-260
36. Remark:, The exact citations are: "time is on my side" and "I can get no satisfaction". The reader may have guessed that the title of this review could have been: "UCPs like a rolling stone".
37. Schrauwen P., Saris W.H., and Hesselink M.K. An alternative function for human uncoupling protein 3: protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix. FASEB J. 15 (2001) 2497-2502
38. Garcia-Martinez C., Sibille B., Solanes G., Darimont C., Mace K., Villarroya F., and Gomez-Foix A.M. Overexpression of UCP3 in cultured human muscle lowers mitochondrial membrane potential, raises ATP/ADP ratio, and favors fatty acid vs. glucose oxidation. FASEB J. 15 (2001) 2033-2035
39. Harper M.E., Antoniou A., Villalobos-Menuey E., Russo A., Trauger R., Vendemelio M., George A., Bartholomew R., Carlo D., Shaikh A., Kupperman J., Newell E.W., Bespalov I.A., Wallace S.S., Liu Y., Rogers J.R., Gibbs G.L., Leahy J.L., Camley R.E., Melamede R., and Newell M.K. Characterization of a novel metabolic strategy used by drug-resistant tumor cells. Faseb. J. 16 (2002) 1550-1557
40. Nedergaard J., Bengtsson T., and Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol., Endocrinol. Metab. 293 (2007) E444-452
41. Hesselink M.K., Keizer H.A., Borghouts L.B., Schaart G., Kornips C.F., Slieker L.J., Sloop K.W., Saris W.H., and Schrauwen P. Protein expression of UCP3 differs between human type 1, type 2a, and type 2b fibers. FASEB J. 15 (2001) 1071-1073
42. Pecqueur C., Alves-Guerra M.C., Gelly C., Levi-Meyrueis C., Couplan E., Collins S., Ricquier D., Bouillaud F., and Miroux B. Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation. J. Biol. Chem. 276 (2001) 8705-8712
43. Schrauwen P., and Hesselink M.K. The role of uncoupling protein 3 in fatty acid metabolism: protection against lipotoxicity?. Proc. Nutr. Soc. 63 (2004) 287-292
44. Ainscow E.K., and Brand M.D. Internal regulation of ATP turnover, glycolysis and oxidative phosphorylation in rat hepatocytes. Eur. J. Biochem. 266 (1999) 737-749
45. Samudio I., Fiegl M., McQueen T., Clise-Dwyer K., and Andreeff M. The warburg effect in leukemia-stroma cocultures is mediated by mitochondrial uncoupling associated with uncoupling protein 2 activation. Cancer Res. 68 (2008) 5198-5205
46. Zhang C.Y., Parton L.E., Ye C.P., Krauss S., Shen R., Lin C.T., Porco Jr. J.A., and Lowell B.B. Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets. Cell. Metab. 3 (2006) 417-427
47. Jezek P., and Garlid K.D. New substrates and competitive inhibitors of the Cl-translocating pathway of the uncoupling protein of brown adipose tissue mitochondria. J. Biol. Chem. 265 (1990) 19303-19311
48. Echtay K.S., Liu Q., Caskey T., Winkler E., Frischmuth K., Bienengraber M., and Klingenberg M. Regulation of UCP3 by nucleotides is different from regulation of UCP1. FEBS Lett. 450 (1999) 8-12
49. Brand M.D., Pamplona R., Portero-Otin M., Requena J.R., Roebuck S.J., Buckingham J.A., Clapham J.C., and Cadenas S. Oxidative damage and phospholipid fatty acyl composition in skeletal muscle mitochondria from mice underexpressing or overexpressing uncoupling protein 3. Biochem. J. 368 (2002) 597-603
50. Emre Y., Hurtaud C., Nubel T., Criscuolo F., Ricquier D., and Cassard-Doulcier A.M. Mitochondria contribute to LPS-induced MAPK activation via uncoupling protein UCP2 in macrophages. Biochem. J. 402 (2007) 271-278
51. Lacy-Hulbert A., and Moore K.J. Designer macrophages: oxidative metabolism fuels inflammation repair. Cell. Metab. 4 (2006) 7-8
52. Cannon B., Shabalina I.G., Kramarova T.V., Petrovic N., and Nedergaard J. Uncoupling proteins: a role in protection against reactive oxygen species-or not?. Biochim. Biophys. Acta 1757 (2006) 449-458
53. Diano S., Matthews R.T., Patrylo P., Yang L., Beal M.F., Barnstable C.J., and Horvath T.L. Uncoupling protein 2 prevents neuronal death including that occurring during seizures: a mechanism for preconditioning. Endocrinology 144 (2003) 5014-5021
54. Hoerter J., Gonzalez-Barroso M.D., Couplan E., Mateo P., Gelly C., Cassard-Doulcier A.M., Diolez P., and Bouillaud F. Mitochondrial uncoupling protein 1 expressed in the heart of transgenic mice protects against ischemic-reperfusion damage. Circulation 110 (2004) 528-533
55. Johnson-Cadwell L.I., Jekabsons M.B., Wang A., Polster B.M., and Nicholls D.G. 'Mild Uncoupling' does not decrease mitochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress. J. Neurochem. 101 (2007) 1619-1631
56. Serviddio G., Bellanti F., Tamborra R., Rollo T., Capitanio N., Romano A.D., Sastre J., Vendemiale G., and Altomare E. Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury. Gut 57 (2008) 957-965
57. Skulachev V.P. Uncoupling: new approaches to an old problem of bioenergetics. Biochim. Biophys. Acta 1363 (1998) 100-124
58. Mills E.M., Banks M.L., Sprague J.E., and Finkel T. Pharmacology: uncoupling the agony from ecstasy. Nature 426 (2003) 403-404