scholarly journals Transport of anions and protons by the mitochondrial uncoupling protein and its regulation by nucleotides and fatty acids. A new look at old hypotheses

1994 ◽  
Vol 269 (42) ◽  
pp. 26184-26190
Author(s):  
P Jezek ◽  
D E Orosz ◽  
M Modriansky ◽  
K D Garlid
Keyword(s):  
Fatty Acids ◽  
Uncoupling Protein ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
New Look

scholarly journals Mitochondrial uncoupling protein may participate in futile cycling of pyruvate and other monocarboxylates

1998 ◽  
Vol 275 (2) ◽  
pp. C496-C504 ◽  
Author(s):  
Petr Jezek ◽  
Jirí Borecky
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Specific Inhibitor ◽  
Physiological Role ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose ◽  
Futile Cycling

The physiological role of monocarboxylate transport in brown adipose tissue mitochondria has been reevaluated. We studied pyruvate, α-ketoisovalerate, α-ketoisocaproate, and phenylpyruvate uniport via the uncoupling protein (UCP1) as a GDP-sensitive swelling in K+ salts induced by valinomycin or by monensin and carbonyl cyanide- p-(trifluoromethoxy)phenylhydrazone in Na+ salts. We have demonstrated that this uniport is inhibited by fatty acids. GDP inhibition in K+ salts was not abolished by an uncoupler, indicating a negligible monocarboxylic acid penetration via the lipid bilayer. In contrast, the electroneutral pyruvate uptake (swelling in ammonium pyruvate or potassium pyruvate induced by change in pH) mediated by the pyruvate carrier was inhibited by its specific inhibitor α-cyano-4-hydroxycinnamate but not by fatty acids. Moreover, α-cyano-4-hydroxycinnamate enhanced the energization of brown adipose tissue mitochondria, which was monitored fluorometrically by 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide and safranin O. Consequently, we suggest that UCP1 might participate in futile cycling of unipolar ketocarboxylates under certain physiological conditions while expelling these anions from the matrix. The cycle is completed on their return via the pyruvate carrier in an H+ symport mode.

scholarly journals The mitochondrial uncoupling protein from guinea-pig brown adipose tissue. Synchronous increase in structural and functional parameters during cold-adaptation

1984 ◽  
Vol 222 (3) ◽  
pp. 685-693 ◽  
Author(s):  
E Rial ◽  
D G Nicholls
Keyword(s):  
Fatty Acids ◽  
Time Course ◽  
Binding Capacity ◽  
Uncoupling Protein ◽  
Nucleotide Binding ◽  
Mitochondrial Uncoupling ◽  
Functional Parameters ◽  
Nucleotide Binding Sites ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

The time-course for the induction of the uncoupling pathway in the inner membrane of brown-fat mitochondria from cold-adapting guinea pigs was studied. The amount of the protein was quantified from the capacity for high-affinity binding of GDP to the intact mitochondria, and was compared with the functional parameters diagnostic of the protein, namely the nucleotide-sensitive proton conductance and the sensitivity to uncoupling by low concentrations of fatty acids. A monophasic increase in nucleotide titre was observed, with no evidence of an early ‘unmasking’ of preexisting nucleotide-binding sites. The nucleotide-sensitive conductance increased in precise synchrony with the nucleotide-binding capacity. Mitochondria from newborn animals, and those from acutely cold-adapted animals, showed anomalously low sensitivities to uncoupling by fatty acids.

scholarly journals Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Hongshan Ge ◽  
Fan Zhang ◽  
Dan Shan ◽  
Hua Chen ◽  
Xiaona Wang ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Uncoupling Protein ◽  
Physiological Role ◽  
Cumulus Cells ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Cultural Medium ◽  
Cellular Autophagy ◽  
Significant Difference ◽  
Active Caspase

UCP2 plays a physiological role by regulating mitochondrial biogenesis, maintaining energy balance, ROS elimination, and regulating cellular autophagy in numerous tissues. But the exact roles of UCP2 in cumulus cells are still not clear. Genipin, a special UCP2 inhibitor, was added into the cultural medium to explore the roles of UCP2 in human cumulus cells. There were no significant differences in ATP and mitochondrial membrane potential levels in cumulus cells from UCP2 inhibiting groups as compared with the control. The levels of ROS and Mn-SOD were markedly elevated after UCP2 inhibited Genipin. However, the ratio of reduced GSH to GSSG significantly declined after treatment with Genipin. UCP2 inhibition by Genipin also resulted in obvious increase in the active caspase-3, which accompanied the decline of caspase-3 mRNA. The level of progesterone in culture medium declined obviously after Genipin treatment. But there was no significant difference in estradiol concentrations. This study indicated that UCP2 is expressed in human cumulus cells and plays important roles on mediate ROS production, apoptotic process, and steroidogenesis, suggesting UCP2 may be involved in regulation of follicle development and oocyte maturation and quality.

scholarly journals Mitochondrial Hormesis in PancreaticβCells: Does Uncoupling Protein 2 Play a Role?

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Ning Li ◽  
Suzana Stojanovski ◽  
Pierre Maechler
Keyword(s):  
Stress Responses ◽  
Defense Mechanisms ◽  
Defense Mechanism ◽  
Cell Function ◽  
Uncoupling Protein ◽  
Glucose Sensing ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Cellular Stresses ◽  
Excessive Nutrients

In pancreaticβcells, mitochondrial metabolism translates glucose sensing into signals regulating insulin secretion. Chronic exposure ofβcells to excessive nutrients, namely, glucolipotoxicity, impairsβ-cell function. This is associated with elevated ROS production from overstimulated mitochondria. Mitochondria are not only the major source of cellular ROS, they are also the primary target of ROS attacks. The mitochondrial uncoupling protein UCP2, even though its uncoupling properties are debated, has been associated with protective functions against ROS toxicity. Hormesis, an adaptive response to cellular stresses, might contribute to the protection againstβ-cell death, possibly limiting the development of type 2 diabetes. Mitochondrial hormesis, or mitohormesis, is a defense mechanism observed in ROS-induced stress-responses by mitochondria. Inβcells, mitochondrial damages induced by sublethal exogenous H2O2can induce secondary repair and defense mechanisms. In this context, UCP2 is a marker of mitohormesis, being upregulated following stress conditions. When overexpressed in nonstressed naïve cells, UCP2 confers resistance to oxidative stress. Whether treatment with mitohormetic inducers is sufficient to restore or ameliorate secretory function ofβcells remains to be determined.

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