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

Komelina, Natalia P.; Amerkhanov, Z. G.

doi:10.18388/abp.2010_2427

Cited by 7 publications

(11 citation statements)

References 31 publications

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“…The inhibitory effect of CATR towards other carrier (citrate carrier) than ANT has also been reported [50]. However, it has also been reported that CATR does not influence the GDP binding to UCP2 [12] and does not inhibit UCP1 action [34]. In summary, if CATR and GDP are not specific for their classical targets, measurements focused on UCP inhibition should not be performed in the presence of GDP and CATR.…”

Section: Resultsmentioning

confidence: 99%

Different Effects of Guanine Nucleotides (GDP and GTP) on Protein-Mediated Mitochondrial Proton Leak

Woyda-Płoszczyca

Jarmuszkiewicz

2014

PLoS ONE

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In this study, we compared the influence of GDP and GTP on isolated mitochondria respiring under conditions favoring oxidative phosphorylation (OXPHOS) and under conditions excluding this process, i.e., in the presence of carboxyatractyloside, an adenine nucleotide translocase inhibitor, and/or oligomycin, an FOF1-ATP synthase inhibitor. Using mitochondria isolated from rat kidney and human endothelial cells, we found that the action of GDP and GTP can differ diametrically depending on the conditions. Namely, under conditions favoring OXPHOS, both in the absence and presence of linoleic acid, an activator of uncoupling proteins (UCPs), the addition of 1 mM GDP resulted in the state 4 (non-phosphorylating respiration)-state 3 (phosphorylating respiration) transition, which is characteristic of ADP oxidative phosphorylation. In contrast, the addition of 1 mM GTP resulted in a decrease in the respiratory rate and an increase in the membrane potential, which is characteristic of UCP inhibition. The stimulatory effect of GDP, but not GTP, was also observed in inside-out submitochondrial particles prepared from rat kidney mitochondria. However, the effects of GDP and GTP were more similar in the presence of OXPHOS inhibitors. The importance of these observations in connection with the action of UCPs, adenine nucleotide translocase (or other carboxyatractyloside-sensitive carriers), carboxyatractyloside- and purine nucleotide-insensitive carriers, as well as nucleoside-diphosphate kinase (NDPK) are considered. Because the measurements favoring oxidative phosphorylation better reflect in vivo conditions, our study strongly supports the idea that GDP cannot be considered a significant physiological inhibitor of UCP. Moreover, it appears that, under native conditions, GTP functions as a more efficient UCP inhibitor than GDP and ATP.

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Section: Resultsmentioning

confidence: 99%

Different Effects of Guanine Nucleotides (GDP and GTP) on Protein-Mediated Mitochondrial Proton Leak

Woyda-Płoszczyca

Jarmuszkiewicz

2014

PLoS ONE

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“…Both UCP-1 and ANT can be inhibited by purine nucleotides such as GDP [ 107 ]. The binding of GDP to UCP-1 is dependent on pH and is optimal at pH 7.0.…”

Section: Mitochondrial Uncoupling Proteins and Metabolites Crosstamentioning

confidence: 99%

“…As demonstrated in isolated rat muscle cells, this effect might rely on superoxide anion production, NFκB activation and iNOS induction (NO production) [ 117 ]. However, the role of UCP-3 as a functional uncoupling protein is still debated and controversial [ 107 ]. Another mechanism by which FFAs could control mitochondrial uncoupling in brown adipocytes is through a direct effect on UCP-1.…”

Section: Mitochondrial Uncoupling Proteins and Metabolites Crosstamentioning

confidence: 99%

“…This effect might rely on superoxide anion production, NFκB activation and iNOS induction (NO production), as demonstrated in isolated rat muscle cells [ 117 ]. However, it should be mentioned that the role of UCP-3 as a functional uncoupling protein is still debated and controversial [ 107 ].…”

Section: Mitochondrial Uncoupling Proteins and Metabolites Crosstamentioning

confidence: 99%

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Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches

et al. 2014

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Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic.

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“…4 Recently, GDP inhibition of proton leak was reported. 5 One mM GDP stimulation of respiration and decrease of the membrane potential in isolated mitochondria were observed. 6 Cyclic nucleoside diphosphate ribose, such as cyclic adenosine 5 0 -diphosphate ribose (cADPR), a potent intracellular-Ca 2+ -mobilizing second messenger, is produced enzymatically from nicotinamide adenine dinucleotide (NAD + ) by ADP-ribosyl cyclases.…”

mentioning

confidence: 98%

A review on the chemical synthesis of pyrophosphate bonds in bioactive nucleoside diphosphate analogs

2015

Bioorganic & Medicinal Chemistry Letters

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

Cited by 7 publications

References 31 publications

Different Effects of Guanine Nucleotides (GDP and GTP) on Protein-Mediated Mitochondrial Proton Leak

Different Effects of Guanine Nucleotides (GDP and GTP) on Protein-Mediated Mitochondrial Proton Leak

Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches

A review on the chemical synthesis of pyrophosphate bonds in bioactive nucleoside diphosphate analogs

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