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2010 | 57 | 4 | 413-419
Article title

A comparative study of the inhibitory effects of purine nucleotides and carboxyatractylate on the uncoupling protein-3 and adenine nucleotide translocase

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EN
Abstracts
EN
Uncoupling proteins (UCPs) mediate fatty acid-induced proton cycling in mitochondria, which is stimulated by superoxide and inhibited by GDP. Fatty acid anions can also be transported by adenine nucleotide translocase (ANT), thus resulting in the uncoupling of oxidative phosphorylation. In the present work, an attempt was made to distinguish between the protonophoric activity of UCP3 and that of ANT using inhibition analysis. This study was carried out using mitochondria from skeletal muscles of hibernating Yakut ground squirrel, which have a significant level of UCP3 mRNA. We found that millimolar concentrations of GDP, which is considered to be a specific inhibitor of UCPs, slightly recoupled the mitochondrial respiration and restored the membrane potential. Addition of the specific ANT inhibitor CAT (carboxyatractylate), in micromolar concentration, prior to GDP prevented its recoupling effect. Moreover, GDP and ADP exhibited a competitive kinetic behavior with respect to ANT. In brown adipose tissue, CAT did not prevent the UCP1-iduced increase in chloride permeability and the inhibitory effect of GDP, thus confirming the inability of CAT to affect UCP1. These results allow us to conclude that the recoupling effect of purine nucleotides on skeletal muscle mitochondria of hibernating ground squirrels can be explained by interaction of the nucleotides with ANT, whereas UCP3 is not involved in the process.
Publisher

Year
Volume
57
Issue
4
Pages
413-419
Physical description
Dates
published
2010
received
2010-08-31
revised
2010-10-05
accepted
2010-11-20
(unknown)
2010-12-10
Contributors
  • Laboratory of Mechanisms of Natural Hypometabolic States, Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia
References
  • Andreyev A, Bondareva TO, Dedukhova VI, Mokhova EN, Skulachev VP, Tsofina LM, Volkov NI, Vygodina TV (1989) The ATP/ADP-antiporter is involved in the uncoupling effect of fatty acids on mitochondria. Eur J Biochem 182: 585-592.
  • Barger JL, Barnes BM, Boyer BB (2006) Regulation of UCP1 and UCP3 in arctic ground squirrels and relation with mitochondrial proton leak. J Appl Physiol 101: 339-347.
  • Boss O, Samec A, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, Muzzin P, Giacobino JP (1997) Uncoupling protein-3: A new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett 408: 39-42.
  • Boyer BB, Barnes BM, Lowell BB, Grujic D (1998) Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels. Am J Physiol 275: R1232-R1238.
  • Brustovetsky NN, Amerkanov ZG, Yegorova ME, Mokhova EN, Skulachev VP (1990) Carboxyatractylate-sensitive uncoupling in liver mitochondria from ground squirrels during hibernation and arousal. FEBS Lett 272: 190-192.
  • Brustovetsky NN, Egorova MV, Gnutov DY, Gogvadze VG, Mokhova EN, Skulachev VP (1992) Thermoregulatory, carboxyatractylate - sensitive uncoupling in heart and skeletal muscle mitochondria of the ground squirrel correlates with the level of free fatty acids. FEBS Lett 305: 15-17.
  • Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84: 277-359.
  • Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD (2002) Superoxide activates mitochondrial uncoupling proteins. Nature 415: 96-99.
  • Echtay KS, Esteves TC, Pakay JL, Jekabsons MB, Lambert AJ, Portero-Otin M, Pamplona R, Vidal-Puig AJ, Wang S, Roebuck SJ, Brand MD (2003) A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling. EMBO J 22: 4103-4110.
  • Garlid KD, Orosz DE, 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.
  • Garlid KD, Jaburek M, Jezek P (2001) Mechanism of uncoupling protein action. Biochem Soc Trans 29: 803-806.
  • Goglia F, Skulachev V P (2003) A function for novel uncoupling proteins: antioxidant defense of mitochondrial matrix by translocating fatty acid peroxides from the inner to the outer membrane leaflet. FASEB J 17: 1585-1591.
  • Jaburek M, Varecha M, Gimeno RE, Dembski M, Jezek P, Zhang M, Burn P, Tartaglia LA, Garlid KD (1999) Transport function and regulation of mitochondrial uncoupling proteins 2 and 3. J Biol Chem 274: 26003-26007.
  • Kamo N, Maratsugu M, Hongoh R, Kobatake Y (1979) Membrane potential of mitochondria measured with electrode sensitive to tetraphenilphosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state J Membr Biol 49: 105-121.
  • Khailova LS, Prikhodko EA, Dedukhova VI, Mokhova EN, Popov VN, Skulachev VP (2006) Participation of ATP/ADP antiporter in oleate- and oleate hydroperoxide-induced uncoupling suppressed by GDP and carboxyatractylate. Biochim Biophys Acta 1757: 1324-1329.
  • Klingenberg M (2008) The ADP and ATP transport in mitochondria and its carrier. Biochim Biophys Acta 1778: 1978-2021.
  • Klingenberg M, Echtay KS (2001) Uncoupling proteins: issues from a biochemist point of view. Biochim Biophys Acta 1504: 128-143.
  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408.
  • Mak IT, Shrago E, Elson CE (1983) The influence of linoleic acid intake on the kinetics of adenine nucleotide translocase. Lipids 18: 130-136.
  • Nedergaard J, Cannon B (2003) The 'novel' 'uncoupling' proteins UCP2 and UCP3: what do they really do? Pros and cons for suggested functions. Exp Physiol 88: 65-84.
  • Nicholls DG (1979) Brown adipose tissue mitochondria. Biochim Biophys Acta 549: 1-29.
  • Parker N, Affourtit C, Vidal-Puig A, Brand MD (2008) Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria. Biochem J 412: 131-139.
  • Ricquier D, Bouillaud F (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J 345: 161-179.
  • Samartsev VN, Smirnov AV, Zeldi IP, Markova OV, Mokhova EN, Skulachev VP (1997) Involvement of aspartate/glutamate antiporter in fatty acid-induced uncoupling of liver mitochondria. Biochim Biophys Acta 1319: 251-257.
  • Simonyan RA, Skulachev VP (1998) Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein. FEBS Lett 436: 81-84.
  • Skulachev VP (1991) Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation. FEBS Lett 294: 158-162.
  • Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V, Cortright R, Muoio DM, Lowell BB (2000) Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem 275: 16258-16266.
  • Wanders RJA, Groen AK, Van Roermund CWT, Tager JM (1984) Factors determining the relative contribution of the adenine-nucleotide translocator and the ADP-regenerating system to the control of oxidative phosphorylation in isolated rat-liver mitochondria. Eur J Biochem 142: 417-424.
  • Wieckowski MR, Wojtczak L (1997) Involvement of the dicarboxylate carrier in the protonophoric action of long-chain fatty acids in mitochondria. Biochem Biophys Res Commun 232: 414-417.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv57p413kz
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