Loss of UCP2 Attenuates Mitochondrial Dysfunction without Altering ROS Production and Uncoupling Activity

PLoS Genetics

Volumn 10, Issue 6, 2014, Pages

  Kukat, Alexandra ^a,b   Dogan, Sukru Anil ^a   Edgar, Daniel ^b   Mourier, Arnaud ^c   Jacoby, Christoph ^d   Maiti, Priyanka ^a   Mauer, Jan ^e   Becker, Christina ^a   Senft, Katharina ^a   Wibom, Rolf ^b   Kudin, Alexei P ^f   Hultenby, Kjell ^b   Flögel, Ulrich ^d   Rosenkranz, Stephan ^g   Ricquier, Daniel ^h   Kunz, Wolfram S ^f   Trifunovic, Aleksandra ^a,b,g  

^a UNIVERSITY OF COLOGNE   (Germany)

^b KAROLINSKA INSTITUTE   (Sweden)

^c MAX PLANCK INSTITUTE FOR BIOLOGY OF AGEING   (Germany)

^d HEINRICH HEINE UNIVERSITY   (Germany)

^e MAX PLANCK INSTITUTE FOR NEUROLOGICAL RESEARCH   (Germany)

^f UNIVERSITY OF BONN   (Germany)

^g UNIVERSITY OF COLOGNE   (Germany)

^h UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

MITOCHONDRIAL DNA; REACTIVE OXYGEN METABOLITE; UNCOUPLING PROTEIN 2; FATTY ACID; ION CHANNEL; MITOCHONDRIAL PROTEIN; MITOCHONDRIAL UNCOUPLING PROTEIN 2; PROTON PUMP;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATTENUATION; BODY MASS; CARDIOMYOPATHY; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENERGY METABOLISM; FATTY ACID OXIDATION; FEMALE; HEART MITOCHONDRION; LACTIC ACIDOSIS; LIFESPAN; MALE; MITOCHONDRIAL RESPIRATION; MOUSE; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION; UPREGULATION; ANIMAL; C57BL MOUSE; EATING; GENETICS; HEART MUSCLE; KNOCKOUT MOUSE; LIFE EXPECTANCY; METABOLISM; OXIDATION REDUCTION REACTION; PATHOLOGY;

ACIDOSIS, LACTIC; ANIMALS; CARDIOMYOPATHIES; EATING; ENERGY METABOLISM; FATTY ACIDS; ION CHANNELS; LIFE EXPECTANCY; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MITOCHONDRIA, HEART; MITOCHONDRIAL DISEASES; MITOCHONDRIAL PROTEINS; MYOCARDIUM; OXIDATION-REDUCTION; OXIDATIVE STRESS; PROTON PUMPS; REACTIVE OXYGEN SPECIES;

EID: 84903469647     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1004385     Document Type: Article

References (53)

1. Harman D, (1973) Free radical theory of aging. Triangle 12: 153-158.
2. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, et al. (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429: 417-423.
3. Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, et al. (2005) Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci U S A 102: 17993-17998.
4. Brand MD, (2000) Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 35: 811-820.
5. Shabalina IG, Nedergaard J, (2011) Mitochondrial ('mild') uncoupling and ROS production: physiologically relevant or not? Biochem Soc Trans 39: 1305-1309.
6. Rousset S, Alves-Guerra MC, Mozo J, Miroux B, Cassard-Doulcier AM, et al. (2004) The biology of mitochondrial uncoupling proteins. Diabetes 53Suppl 1: S130-135.
7. Cannon B, Shabalina IG, Kramarova TV, Petrovic N, Nedergaard J, (2006) Uncoupling proteins: a role in protection against reactive oxygen species-or not? Biochim Biophys Acta 1757: 449-458.
8. Bechmann I, Diano S, Warden CH, Bartfai T, Nitsch R, et al. (2002) Brain mitochondrial uncoupling protein 2 (UCP2): a protective stress signal in neuronal injury. Biochem Pharmacol 64: 363-367.
9. Fridell YW, Sanchez-Blanco A, Silvia BA, Helfand SL, (2005) Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly. Cell Metab 1: 145-152.
10. Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, et al. (2001) Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105: 745-755.
11. Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, et al. (2000) Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 406: 415-418.
12. Pecqueur C, Alves-Guerra MC, Gelly C, Levi-Meyrueis C, Couplan E, et al. (2001) Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation. J Biol Chem 276: 8705-8712.
13. Couplan E, del Mar Gonzalez-Barroso M, Alves-Guerra MC, Ricquier D, Goubern M, et al. (2002) 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: 26268-26275.
14. Andrews ZB, Horvath TL, (2009) Uncoupling protein-2 regulates lifespan in mice. Am J Physiol Endocrinol Metab 296: E621-627.
15. Diano S, Horvath TL, (2012) Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. Trends Mol Med 18: 52-58.
16. Pecqueur C, Alves-Guerra C, Ricquier D, Bouillaud F, (2009) UCP2, a metabolic sensor coupling glucose oxidation to mitochondrial metabolism? IUBMB Life 61: 762-767.
17. Pi J, Bai Y, Daniel KW, Liu D, Lyght O, et al. (2009) Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology 150: 3040-3048.
18. Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, et al. (2008) UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. Nature 454: 846-851.
19. Chaudhri O, Small C, Bloom S, (2006) Gastrointestinal hormones regulating appetite. Philos Trans R Soc Lond B Biol Sci 361: 1187-1209.
20. Schwartz DR, Lazar MA, (2011) Human resistin: found in translation from mouse to man. Trends Endocrinol Metab 22: 259-265.
21. Baggio LL, Drucker DJ, (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132: 2131-2157.
22. De Taeye B, Smith LH, Vaughan DE, (2005) Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease. Curr Opin Pharmacol 5: 149-154.
23. Sebastiani M, Giordano C, Nediani C, Travaglini C, Borchi E, et al. (2007) Induction of mitochondrial biogenesis is a maladaptive mechanism in mitochondrial cardiomyopathies. J Am Coll Cardiol 50: 1362-1369.
24. Wang J, Wilhelmsson H, Graff C, Li H, Oldfors A, et al. (1999) Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Nat Genet 21: 133-137.
25. Tyynismaa H, Carroll CJ, Raimundo N, Ahola-Erkkila S, Wenz T, et al. (2010) Mitochondrial myopathy induces a starvation-like response. Hum Mol Genet 19: 3948-3958.
26. Planavila A, Redondo I, Hondares E, Vinciguerra M, Munts C, et al. (2013) Fibroblast growth factor 21 protects against cardiac hypertrophy in mice. Nat Commun 4: 2019.
27. Dogan SA, Pujol C, Maiti P, Kukat A, Wang S, et al. (2014) Tissue-Specific Loss of DARS2 Activates Stress Responses Independently of Respiratory Chain Deficiency in the Heart. Cell Metab 19: 458-469.
28. Potthoff MJ, Kliewer SA, Mangelsdorf DJ, (2012) Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Dev 26: 312-324.
29. Ahlqvist KJ, Hamalainen RH, Yatsuga S, Uutela M, Terzioglu M, et al. (2012) Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice. Cell Metab 15: 100-109.
30. Abel ED, Doenst T, (2011) Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovasc Res 90: 234-242.
31. Storch J, Thumser AE, (2010) Tissue-specific functions in the fatty acid-binding protein family. J Biol Chem 285: 32679-32683.
32. Schaap FG, van der Vusse GJ, Glatz JF, (1998) Fatty acid-binding proteins in the heart. Mol Cell Biochem 180: 43-51.
33. Sugden MC, Holness MJ, (2003) Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab 284: E855-862.
34. Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Manning BS, et al. (2000) Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet 26: 435-439.
35. Pecqueur C, Bui T, Gelly C, Hauchard J, Barbot C, et al. (2008) Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization. FASEB J 22: 9-18.
36. Jezek P, Engstova H, Zackova M, Vercesi AE, Costa AD, et al. (1998) Fatty acid cycling mechanism and mitochondrial uncoupling proteins. Biochim Biophys Acta 1365: 319-327.
37. Vozza A, Parisi G, De Leonardis F, Lasorsa FM, Castegna A, et al. (2014) UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation. Proc Natl Acad Sci U S A 111: 960-965.
38. Wende AR, Abel ED, (2010) Lipotoxicity in the heart. Biochim Biophys Acta 1801: 311-319.
39. Abdul-Ghani MA, Muller FL, Liu Y, Chavez AO, Balas B, et al. (2008) Deleterious action of FA metabolites on ATP synthesis: possible link between lipotoxicity, mitochondrial dysfunction, and insulin resistance. Am J Physiol Endocrinol Metab 295: E678-685.
40. Opie LH, Knuuti J, (2009) The adrenergic-fatty acid load in heart failure. J Am Coll Cardiol 54: 1637-1646.
41. Neubauer S, (2007) The failing heart-an engine out of fuel. N Engl J Med 356: 1140-1151.
42. Dimauro S, Mancuso M, Naini A, (2004) Mitochondrial encephalomyopathies: therapeutic approach. Ann N Y Acad Sci 1011: 232-245.
43. Ogasawara E, Nakada K, Hayashi J, (2010) Lactic acidemia in the pathogenesis of mice carrying mitochondrial DNA with a deletion. Hum Mol Genet 19: 3179-3189.
44. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, et al. (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309: 481-484.
45. Dai DF, Chen T, Wanagat J, Laflamme M, Marcinek DJ, et al. (2010) Age-dependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria. Aging Cell 9: 536-544.
46. Shabalina IG, Petrovic N, Kramarova TV, Hoeks J, Cannon B, et al. (2006) UCP1 and defense against oxidative stress. 4-Hydroxy-2-nonenal effects on brown fat mitochondria are uncoupling protein 1-independent. J Biol Chem 281: 13882-13893.
47. Silva JP, Shabalina IG, Dufour E, Petrovic N, Backlund EC, et al. (2005) SOD2 overexpression: enhanced mitochondrial tolerance but absence of effect on UCP activity. Embo J 24: 4061-4070.
48. Espie P, Guerin B, Rigoulet M, (1995) On isolated hepatocytes mitochondrial swelling induced in hypoosmotic medium does not affect the respiration rate. Biochim Biophys Acta 1230: 139-146.
49. Mourier A, Devin A, Rigoulet M, (2009) Active proton leak in mitochondria: a new way to regulate substrate oxidation. Biochim Biophys Acta 1797: 255-261.
50. Sciacco M, Bonilla E, (1996) Cytochemistry and immunocytochemistry of mitochondria in tissue sections. Methods Enzymol 264: 509-521.
51. Wibom R, Hagenfeldt L, von Döbeln U, (2002) Measurement of ATP production and respiratory chain enzyme activities in mitochondria isolated from small muscle biopsy samples. Anal Biochem 311: 139-151.
52. Mourier A, Ruzzenente B, Brandt T, Kuhlbrandt W, Larsson NG, (2014) Loss of LRPPRC causes ATP synthase deficiency. Hum Mol Genet 10: 2580-2592.
53. Jacoby C, Molojavyi A, Flogel U, Merx MW, Ding Z, et al. (2006) Direct comparison of magnetic resonance imaging and conductance microcatheter in the evaluation of left ventricular function in mice. Basic Res Cardiol 101: 87-95.