scholarly journals Thyroid-hormone control of state-3 respiration in isolated rat liver mitochondria

1990 ◽  
Vol 265 (3) ◽  
pp. 731-734 ◽  
Author(s):  
R P Hafner ◽  
G C Brown ◽  
M D Brand
Keyword(s):  
Thyroid Hormone ◽  
Atp Synthase ◽  
Adenine Nucleotide ◽  
Liver Mitochondria ◽  
Proton Leak ◽  
Rat Liver Mitochondria ◽  
Protonmotive Force ◽  
Adenine Nucleotide Translocator ◽  
Hormone Control ◽  
Kinetics Of

Oxidative phosphorylation can be treated as two groups of reactions; those that generate protonmotive force (dicarboxylate carrier, succinate dehydrogenase and the respiratory chain) and those that consume protonmotive force (adenine nucleotide and phosphate carriers. ATP synthase and proton leak). Mitochondria from hypothyroid rats have lower rates of respiration in the presence of ADP (state 3) than euthyroid controls. We show that the kinetics of the protonmotive-force generators are unchanged in mitochondria from hypothyroid animals, but the kinetics of the protonmotive-force consumers are altered, supporting proposals that the important effects of thyroid hormone on state 3 are on the ATP synthase or the adenine nucleotide translocator.

Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding

2000 ◽  
Vol 349 (2) ◽  
pp. 519-526 ◽  
Author(s):  
Ausra MARCINKEVICIUTE ◽  
Vida MILDAZIENE ◽  
Sara CRUMM ◽  
Oleg DEMIN ◽  
Jan B. HOEK ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Rat Liver ◽  
Liver Mitochondria ◽  
Proton Leak ◽  
Rat Liver Mitochondria ◽  
Protonmotive Force ◽  
Compensatory Mechanisms ◽  
Mitochondrial Energy Metabolism ◽  
Ethanol Feeding ◽  
And Control

Changes in the kinetics and regulation of oxidative phosphorylation were characterized in isolated rat liver mitochondria after 2 months of ethanol consumption. Mitochondrial energy metabolism was conceptually divided into three groups of reactions, either producing protonmotive force (∆p) (the respiratory subsystem) or consuming it (the phosphorylation subsystem and the proton leak). Manifestation of ethanol-induced mitochondrial malfunctioning of the respiratory subsystem was observed with various substrates; the respiration rate in State 3 was inhibited by 27±4% with succinate plus amytal, by 20±4% with glutamate plus malate, and by 17±2% with N,N,Nʹ,Nʹ-tetramethyl-p-phenylenediamine/ascorbate. The inhibition of the respiratory activity correlated with the lower activities of cytochrome c oxidase, the bc1 complex, and the ATP synthase in mitochondria of ethanol-fed rats. The block of reactions consuming the ∆p to produce ATP (the phosphorylating subsystem) was suppressed after 2 months of ethanol feeding, whereas the mitochondrial proton leak was not affected. The contributions of ∆p supply (the respiratory subsystem) and ∆p demand (the phosphorylation and the proton leak) to the control of the respiratory flux were quantified as the control coefficients of these subsystems. In State 3, the distribution of control exerted by different reaction blocks over respiratory flux was not significantly affected by ethanol diet, despite the marked changes in the kinetics of individual functional units of mitochondrial oxidative phosphorylation. This suggests the operation of compensatory mechanisms, when control redistributes among the different components within the same subsystem.

scholarly journals Control of the effective P/O ratio of oxidative phosphorylation in liver mitochondria and hepatocytes

1993 ◽  
Vol 291 (3) ◽  
pp. 739-748 ◽  
Author(s):  
M D Brand ◽  
M E Harper ◽  
H C Taylor
Keyword(s):  
Oxygen Consumption ◽  
Liver Mitochondria ◽  
Substrate Oxidation ◽  
Proton Leak ◽  
Rat Liver Mitochondria ◽  
Protonmotive Force ◽  
Control Analysis ◽  
Control Coefficient ◽  
Oxidation Reactions ◽  
In Cells

The control exerted by substrate oxidation reactions, by ATP turnover and by the proton leak over the oxygen consumption rate, the phosphorylation rate, the proton leak rate and the protonmotive force (delta p) in isolated rat liver mitochondria under a range of conditions between non-phosphorylating (State 4) and maximum phosphorylation (State 3) was investigated by using the top-down approach of metabolic control analysis. The experiments were carried out with saturating concentrations of the substrates succinate, glutamate with malate, or pyruvate with malate. The distribution of control was very similar with each of the three substrates. The effective P/O ratio (i.e. not corrected for leak reactions) was also measured; it varied from zero in State 4 to 80-90% of the maximum theoretical P/O ratio in State 3. Under most conditions control over the effective P/O ratio was shared between proton leak (which had negative control) and the phosphorylating subsystem (which had roughly equal positive control); near State 4, substrate oxidation reactions also acquired some control over this ratio. In resting hepatocytes the effective P/O ratio was only 50% of its maximum theoretical value, corresponding to an effective P/O ratio of only 1.3 for complete oxidation of glucose. The effective P/O ratio for intracellular mitochondrial oxygen consumption was 64% of the maximum value. The control coefficient of the mitochondrial proton leak over the effective P/O ratio in cells was -0.34; the control coefficient of phosphorylation reactions over this ratio was 0.31 and the control coefficient of substrate oxidation reactions over the ratio was 0.03, showing how the coupling efficiency in cells can respond sensitively to agents that change the proton leak or the ATP demand, but not to those that change substrate oxidation.

scholarly journals Carboxyatractyloside effects on brown-fat mitochondria imply that the adenine nucleotide translocator isoforms ANT1 and ANT2 may be responsible for basal and fatty-acid-induced uncoupling respectively

2006 ◽  
Vol 399 (3) ◽  
pp. 405-414 ◽  
Author(s):  
Irina G. Shabalina ◽  
Tatiana V. Kramarova ◽  
Jan Nedergaard ◽  
Barbara Cannon
Keyword(s):  
Fatty Acid ◽  
Adenine Nucleotide ◽  
Liver Mitochondria ◽  
Basal Respiration ◽  
Brown Fat ◽  
Proton Leak ◽  
Mrna Levels ◽  
Adenine Nucleotide Translocator ◽  
Brown Adipose ◽  
Brown Fat Mitochondria

In brown-fat mitochondria, fatty acids induce thermogenic uncoupling through activation of UCP1 (uncoupling protein 1). However, even in brown-fat mitochondria from UCP1−/− mice, fatty-acid-induced uncoupling exists. In the present investigation, we used the inhibitor CAtr (carboxyatractyloside) to examine the involvement of the ANT (adenine nucleotide translocator) in the mediation of this UCP1-independent fatty-acid-induced uncoupling in brown-fat mitochondria. We found that the contribution of ANT to fatty-acid-induced uncoupling in UCP1−/− brown-fat mitochondria was minimal (whereas it was responsible for nearly half the fatty-acid-induced uncoupling in liver mitochondria). As compared with liver mitochondria, brown-fat mitochondria exhibit a relatively high (UCP1-independent) basal respiration (‘proton leak’). Unexpectedly, a large fraction of this high basal respiration was sensitive to CAtr, whereas in liver mitochondria, basal respiration was CAtr-insensitive. Total ANT protein levels were similar in brown-fat mitochondria from wild-type mice and in liver mitochondria, but the level was increased in brown-fat mitochondria from UCP1−/− mice. However, in liver, only Ant2 mRNA was found, whereas in brown adipose tissue, Ant1 and Ant2 mRNA levels were equal. The data are therefore compatible with a tentative model in which the ANT2 isoform mediates fatty-acid-induced uncoupling, whereas the ANT1 isoform may mediate a significant part of the high basal proton leak in brown-fat mitochondria.

Adenine nucleotide translocator promotes oxidative phosphorylation and mild uncoupling in mitochondria after dexamethasone treatment

2007 ◽  
Vol 293 (5) ◽  
pp. E1320-E1324 ◽  
Author(s):  
Matthieu Arvier ◽  
Laëtitia Lagoutte ◽  
Gyasi Johnson ◽  
Jean-François Dumas ◽  
Benoit Sion ◽  
...  
Keyword(s):  
Atp Synthase ◽  
High Performance ◽  
Adenine Nucleotide ◽  
Uncoupling Protein ◽  
Membrane Surface ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Adenine Nucleotide Translocator ◽  
Dexamethasone Treatment ◽  
Glucocorticoid Treatment

The composition of the mitochondrial inner membrane and uncoupling protein [such as adenine nucleotide translocator (ANT)] contents are the main factors involved in the energy-wasting proton leak. This leak is increased by glucocorticoid treatment under nonphosphorylating conditions. The aim of this study was to investigate mechanisms involved in glucocorticoid-induced proton leak and to evaluate the consequences in more physiological conditions (between states 4 and 3). Isolated liver mitochondria, obtained from dexamethasone-treated rats (1.5 mg·kg−1·day−1), were studied by polarography, Western blotting, and high-performance thin-layer chromatography. We confirmed that dexamethasone treatment in rats induces a proton leak in state 4 that is associated with an increased ANT content, although without any change in membrane surface or lipid composition. Between states 4 and 3, dexamethasone stimulates ATP synthesis by increasing both the mitochondrial ANT and F1-F0 ATP synthase content. In conclusion, dexamethasone increases mitochondrial capacity to generate ATP by modifying ANT and ATP synthase. The side effect is an increased leak in nonphosphorylating conditions.

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