Coenzyme Q induces GDP-sensitive proton conductance in kidney mitochondria

2001 ◽  
Vol 29 (6) ◽  
pp. 763-768 ◽  
Author(s):  
K. S. Echtay ◽  
M. D. Brand
Keyword(s):  
Superoxide Dismutase ◽  
Fatty Acid ◽  
Coenzyme Q10 ◽  
Redox State ◽  
Uncoupling Protein ◽  
Coenzyme Q ◽  
Liver Mitochondria ◽  
Uncoupling Protein 2 ◽  
Proton Conductance ◽  
Kidney Mitochondria

Addition of coenzyme Q10 (CoQ) at low concentration (29 nmol/mg of protein) to kidney but not liver mitochondria resulted in an increase in proton conductance. This uncoupling activity required fatty acid and was completely inhibited by GDP. CoQ activated when it was likely to be reduced but not when it was likely to become oxidized. However, the redox state of endogenous CoQ did not affect mitochondrial proton conductance. Stimulation by CoQ was not inhibited by cyclosporin A, carboxyatractylate, bongkrekate and catalase but could be reversed by superoxide dismutase. We conclude that CoQ acted in mitochondria through production of superoxide, which mediated uncoupling, probably by acting through uncoupling protein 2.

Uncoupling protein‐2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis‐derived pyruvate utilization

2007 ◽  
Vol 22 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Claire Pecqueur ◽  
Thi Bui ◽  
Chantal Gelly ◽  
Julie Hauchard ◽  
Céline Barbot ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Uncoupling Protein 2

scholarly journals Ubiquinone is not required for proton conductance by uncoupling protein 1 in yeast mitochondria

2004 ◽  
Vol 379 (2) ◽  
pp. 309-315 ◽  
Author(s):  
Telma C. ESTEVES ◽  
Karim S. ECHTAY ◽  
Tanya JONASSEN ◽  
Catherine F. CLARKE ◽  
Martin D. BRAND
Keyword(s):  
Proton Transport ◽  
Uncoupling Protein ◽  
Coenzyme Q ◽  
Yeast Mitochondria ◽  
Proton Conductance ◽  
Wild Type ◽  
Uncoupling Protein 1 ◽  
Yeast Saccharomyces Cerevisiae ◽  
Mutant Strains ◽  
Wild Type Yeast

Q (coenzyme Q or ubiquinone) is reported to be a cofactor obligatory for proton transport by UCPs (uncoupling proteins) in liposomes [Echtay, Winkler and Klingenberg (2000) Nature (London) 408, 609–613] and for increasing the binding of the activator retinoic acid to UCP1 [Tomás, Ledesma and Rial (2002) FEBS Lett. 526, 63–65]. In the present study, yeast (Saccharomyces cerevisiae) mutant strains lacking Q and expressing UCP1 were used to determine whether Q was required for UCP function in mitochondria. Wild-type yeast strain and two mutant strains (CENΔCOQ3 and CENΔCOQ2), both not capable of synthesizing Q, were transformed with the mouse UCP1 gene. UCP1 activity was measured as fatty acid-dependent, GDP-sensitive proton conductance in mitochondria isolated from the cells. The activity of UCP1 was similar in both Q-containing and -deficient yeast mitochondria. We conclude that Q is neither an obligatory cofactor nor an activator of proton transport by UCP1 when it is expressed in yeast mitochondria.

Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion

2007 ◽  
Vol 409 (1) ◽  
pp. 199-204 ◽  
Author(s):  
Charles Affourtit ◽  
Martin D. Brand
Keyword(s):  
Insulin Secretion ◽  
Uncoupling Protein ◽  
Proton Leak ◽  
Cell Physiology ◽  
Uncoupling Protein 2 ◽  
Proton Conductance ◽  
Β Cells ◽  
Knock Down ◽  
Glucose Stimulated Insulin Secretion ◽  
Insulinoma Cells

Proton leak exerts stronger control over ATP/ADP in mitochondria from clonal pancreatic β-cells (INS-1E) than in those from rat skeletal muscle, due to the higher proton conductance of INS-1E mitochondria [Affourtit and Brand (2006) Biochem. J. 393, 151–159]. In the present study, we demonstrate that high proton leak manifests itself at the cellular level too: the leak rate (measured as myxothiazol-sensitive, oligomycin-resistant respiration) was nearly four times higher in INS-1E cells than in myoblasts. This relatively high leak activity was decreased more than 30% upon knock-down of UCP2 (uncoupling protein-2) by RNAi (RNA interference). The high contribution of UCP2 to leak suggests that proton conductance through UCP2 accounts for approx. 20% of INS-1E respiration. UCP2 knock-down enhanced GSIS (glucose-stimulated insulin secretion), consistent with a role for UCP2 in β-cell physiology. We propose that the high mitochondrial proton leak in β-cells is a mechanism which amplifies the effect of physiological UCP2 regulators on cytoplasmic ATP/ADP and hence on insulin secretion.

scholarly journals Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation

1997 ◽  
Vol 94 (12) ◽  
pp. 6386-6390 ◽  
Author(s):  
Y.-T. Zhou ◽  
M. Shimabukuro ◽  
K. Koyama ◽  
Y. Lee ◽  
M.-Y. Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Uncoupling Protein 2

Redox state of quinone affects sensitivity of Acanthamoeba castellanii mitochondrial uncoupling protein to purine nucleotides

2008 ◽  
Vol 413 (2) ◽  
pp. 359-367 ◽  
Author(s):  
Aleksandra Swida ◽  
Andrzej Woyda-Ploszczyca ◽  
Wieslawa Jarmuszkiewicz
Keyword(s):  
Respiratory Rate ◽  
Redox State ◽  
Uncoupling Protein ◽  
Acanthamoeba Castellanii ◽  
Inhibitory Effect ◽  
Proton Conductance ◽  
Purine Nucleotides ◽  
Protein Activity ◽  
Mitochondrial Uncoupling ◽  
Quinone Reduction

We studied FFA (free fatty acid)-induced uncoupling activity in Acanthamoeba castellanii mitochondria in the non-phosphorylating state. Either succinate or external NADH was used as a respiratory substrate to determine the proton conductance curves and the relationships between respiratory rate and the quinone reduction level. Our determinations of the membranous quinone reduction level in non-phosphorylating mitochondria show that activation of UCP (uncoupling protein) activity leads to a PN (purine nucleotide)-sensitive decrease in the quinone redox state. The gradual decrease in the rate of quinone-reducing pathways (using titration of dehydrogenase activities) progressively leads to a full inhibitory effect of GDP on LA (linoleic acid) induced proton conductance. This inhibition cannot be attributed to changes in the membrane potential. Indeed, the lack of GDP inhibitory effect observed when the decrease in respiratory rate is accompanied by an increase in the quinone reduction level (using titration of the quinol-oxidizing pathway) proves that the inhibition by nucleotides can be revealed only for a low quinone redox state. It must be underlined that, in A. castellanii non-phosphorylating mitochondria, the transition of the inhibitory effect of GDP on LA-induced UCP-mediated uncoupling is observed for the same range of quinone reduction levels (between 50% and 40%) as that observed previously for phosphorylating conditions. This observation, drawn from the two different metabolic states of mitochondria, indicates that quinone could affect UCP activity through sensitivity to PNs.

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