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Uncoupling proteins UCP2 and UCP3 from mitochondria of liver and skeletal muscle of ground squirrel Spermophilus undulatus do not transport pyruvate in contrast to UCP1 from brown adipose tissue

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Physiological role of mitochondrial uncoupling proteins UCP2 and UCP3, homologous to UCP1 from brown adipose tissue, is unclear. It was proposed recently that UCP2 and UCP3 are metabolic triggers that switch oxidation of glucose to oxidation of fatty acids, exporting pyruvate from mitochondria. In the present study we tried to verify this hypothesis using ground squirrels (Spermophilus undulatus), since expression of all UCPs in different tissues increases during winter season, and UCP1 is abundant in brown fat. We confirmed the possibility of nonspecific transport of pyruvate through UCP1 in brown fat mitochondria and tried to identify similar transport in liver and skeletal muscle mitochondria where UCP2 and UCP3 are expressed. Transport of pyruvate mediated by UCP1 in mitochondria of brown fat was observed using valinomycin-induced swelling of non-respiring mitochondria in 55 mM potassium pyruvate and was inhibited by GDP. In contrast, mitochondria of liver and skeletal muscles in similar conditions did not exhibit electrogenic transport of pyruvate anions that could be related to functioning of UCP2 and UCP3. At the same time, functioning of pyruvate carrier was detected in these mitochondria by nigericin-induced passive swelling or valinomycin-induced active swelling in potassium pyruvate that was inhibited by α-CHC, a specific inhibitor of the pyruvate carrier. Thus, our results suggest that in contrast to UCP1 of brown fat, UCP2 and UCP3 from intact liver and skeletal muscle mitochondria of winter active ground squirrels are unable to carry out pyruvate transport.

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References

  1. Ricquier D., Bouillaud F. 2000. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem. J. 345, 161–179.

    Article  CAS  PubMed  Google Scholar 

  2. Nedergaard J., Cannon B. 2003. The ‘novel’ ‘uncoupling’ protein UCP2 and UCP3: What do they really do? Pros and cons for suggested functions. Exp. Physiol. 88, 65–84.

    Article  CAS  PubMed  Google Scholar 

  3. Nicholls D.G., Locke R.M. 1984. Thermogenic mechanisms in brown fat. Physiol. Rev. 64, 1–64.

    CAS  PubMed  Google Scholar 

  4. Cannon B., Nedergaard J. 2004. Brown adipose tissue: Function and physiological significance. Physiol. Rev. 84, 277–359.

    Article  CAS  PubMed  Google Scholar 

  5. Skulachev V.P. 1991. Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation. FEBS Lett. 294, 158–162.

    Article  CAS  PubMed  Google Scholar 

  6. Garlid K.D., Orosz D.E., Modriansky M., Vassanelli S., Jezek P. 1996. On the mechanism of fatty acid-induced proton transport by mitochondrial uncoupling protein. J. Biol. Chem. 271, 2615–2620.

    Article  CAS  PubMed  Google Scholar 

  7. Jaburek M., Varecha M., Gimeno R.E., Dembski M., Jezek P., Zhang M., Burn P., Tartaglia L.A., Garlid K.D. 1999. Transport function and regulation of mitochondrial uncoupling proteins 2 and 3. J. Biol. Chem. 274, 26003–26007.

    Article  CAS  PubMed  Google Scholar 

  8. Echtay K.S., Winkler E., Frischmuth K., Klingenberg M. 2001. Uncoupling proteins 2 and 3 are highly active H+ transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone). Proc. Natl. Acad. Sci. USA. 98(4), 1416–1421.

    Article  CAS  PubMed  Google Scholar 

  9. Amerhanov Z.G., Komelina (Smirnova) N.P., Markova O.V., Kolaeva S.G., Solomonov N.G. 2004. 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(2), 213–216.

    Article  Google Scholar 

  10. Komelina N.P., Amerkhanov Z.G. 2010. A comparative study of the inhibitory effects of purine nucleotides and carboxyatractylate on the uncoupling protein-3 and adenine nucleotide translocase. Acta Biochimica Polonica. 57(4), 413–419.

    CAS  PubMed  Google Scholar 

  11. Couplan E., Mar Gonzalez-Barroso M., Alves-Guerra M.C., Ricquier D., Goubern M., Bouillaud F. 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.

    Article  CAS  PubMed  Google Scholar 

  12. Pecqueur C., Alves-Guerra C., Ricquier D., Bouillaud F. 2009. UCP2, a metabolic sensor coupling glucose oxidation to mitochondrial metabolism? IUBMB Life. 61(7), 762–767.

    Article  CAS  PubMed  Google Scholar 

  13. Pecqueur C., Bui T., Gelly, C., Hauchard J., Barbot C., Bouillaud F., Ricquier D., Miroux B., Thompson C.B. 2008. Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysisderived pyruvate utilization. FASEB J. 22, 9–18.

    Article  CAS  PubMed  Google Scholar 

  14. Jezek P., Garlid K.D. 1990. New substrates and competitive inhibitors of the Cl-translocating pathway of the uncoupling protein of brown adipose tissue mitochondria. J. Biol. Chem. 265, 19303–19311.

    CAS  PubMed  Google Scholar 

  15. Jezek P., Borecky J. 1998. Mitochondrial uncoupling protein may participate in futile cycling of pyruvate and other monocarboxylates. Am. J. Physiol. 275, C496–C504.

    CAS  PubMed  Google Scholar 

  16. Kalabukhov N.I. 1985. Spiachka mlekopitayushchikh (Hibernation in mammals). Moscow: Nauka.

    Google Scholar 

  17. Boyer B.B., Barnes B.M., Lowell B.B., Grujic D. 1998. Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels. Am. J. Physiol. 275, R1232–R1238.

    CAS  PubMed  Google Scholar 

  18. Staples J.F. Brown J.C.L. 2008. Mitochondrial metabolism in hibernation and daily torpor: A review. J. Comp. Physiol. 178, 811–827.

    Article  CAS  Google Scholar 

  19. Brustovetsky N.N., Amerkanov Z.G., Yegorova M.E., Mohkova E.N., Skulachev V.P. 1990. Carboxyatractylate-sensitive uncoupling in liver mitochondria from ground squirrels during hibernation and arousal. FEBS Lett. 272, 190–192.

    Article  CAS  PubMed  Google Scholar 

  20. Andreyev A., Bondareva T.O., Dedukhova V.I., Mokhova E.N., Skulachev V.P., Tsofina L.M., Volkov N.I., Vygodina T.V. 1989. The ATP/ADP antiporter is involved in the uncoupling effect of fatty acids on mitochondria. Eur. J. Biochem. 182, 585–592.

    Article  PubMed  Google Scholar 

  21. Hittelman K.J., Lindberg O., Cannon B. 1969. Oxidative phosphorylation and compartmentation of fatty acid metabolism in brown fat mitochondria. Eur. J. Biochem. 11(1), 183–192.

    Article  CAS  PubMed  Google Scholar 

  22. Halestrap A.P., Denton R.M. 1974. Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by α-cyano-4-hydroxycinnamate. Biochem. J. 138(2), 313–316.

    CAS  PubMed  Google Scholar 

  23. Harper J.A., Stuart J.A., Jekabsons M.B., Roussel D., Brindle K.M., Dickinson K., Jones R.B., Brand M.D. 2002. Artifactual uncoupling by uncoupling protein 3 in yeast mitochondria at the concentrations found in mouse and rat skeletal-muscle mitochondria. Biochem. J. 361, 49–56.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Science, ul. Institutskaya, 3, Pushchino, Moscow oblast, 142290, Russia

    N. P. Komelina & Z. G. Amerkhanov

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  1. N. P. Komelina
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  2. Z. G. Amerkhanov
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Correspondence to Z. G. Amerkhanov.

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Original Russian Text © N.P. Komelina, Z.G. Amerkhanov, 2013, published in Biologicheskie Membrany, 2013, Vol. 30, No. 5–6, pp. 412–421.

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Komelina, N.P., Amerkhanov, Z.G. Uncoupling proteins UCP2 and UCP3 from mitochondria of liver and skeletal muscle of ground squirrel Spermophilus undulatus do not transport pyruvate in contrast to UCP1 from brown adipose tissue. Biochem. Moscow Suppl. Ser. A 8, 73–81 (2014). https://doi.org/10.1134/S1990747813050073

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  • DOI: https://doi.org/10.1134/S1990747813050073

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