scholarly journals The basal proton conductance of mitochondria depends on adenine nucleotide translocase content

2005 ◽  
Vol 392 (2) ◽  
pp. 353-362 ◽  
Author(s):  
Martin D. Brand ◽  
Julian L. Pakay ◽  
Augustine Ocloo ◽  
Jason Kokoszka ◽  
Douglas C. Wallace ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Metabolic Rate ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Translocase ◽  
Proton Leak ◽  
Proton Conductance ◽  
Wild Type ◽  
Muscle Mitochondria ◽  
Mild Uncoupling ◽  
Molecular Nature

The basal proton conductance of mitochondria causes mild uncoupling and may be an important contributor to metabolic rate. The molecular nature of the proton-conductance pathway is unknown. We show that the proton conductance of muscle mitochondria from mice in which isoform 1 of the adenine nucleotide translocase has been ablated is half that of wild-type controls. Overexpression of the adenine nucleotide translocase encoded by the stress-sensitive B gene in Drosophila mitochondria increases proton conductance, and underexpression decreases it, even when the carrier is fully inhibited using carboxyatractylate. We conclude that half to two-thirds of the basal proton conductance of mitochondria is catalysed by the adenine nucleotide carrier, independently of its ATP/ADP exchange or fatty-acid-dependent proton-leak functions.

scholarly journals Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria

2008 ◽  
Vol 412 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Nadeene Parker ◽  
Charles Affourtit ◽  
Antonio Vidal-Puig ◽  
Martin D. Brand
Keyword(s):  
Skeletal Muscle ◽  
Knockout Mice ◽  
Adenine Nucleotide ◽  
Specific Inhibitor ◽  
Adenine Nucleotide Translocase ◽  
Protonmotive Force ◽  
Proton Conductance ◽  
Wild Type ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria

Leak of protons into the mitochondrial matrix during substrate oxidation partially uncouples electron transport from phosphorylation of ADP, but the functions and source of basal and inducible proton leak in vivo remain controversial. In the present study we describe an endogenous activation of proton conductance in mitochondria isolated from rat and mouse skeletal muscle following addition of respiratory substrate. This endogenous activation increased with time, required a high membrane potential and was diminished by high concentrations of serum albumin. Inhibition of this endogenous activation by GDP [classically considered specific for UCPs (uncoupling proteins)], carboxyatractylate and bongkrekate (considered specific for the adenine nucleotide translocase) was examined in skeletal muscle mitochondria from wild-type and Ucp3-knockout mice. Proton conductance through endogenously activated UCP3 was calculated as the difference in leak between mitochondria from wild-type and Ucp3-knockout mice, and was found to be inhibited by carboxyatractylate and bongkrekate, but not GDP. Proton conductance in mitochondria from Ucp3-knockout mice was strongly inhibited by carboxyatractylate, bongkrekate and partially by GDP. We conclude the following: (i) at high protonmotive force, an endogenously generated activator stimulates proton conductance catalysed partly by UCP3 and partly by the adenine nucleotide translocase; (ii) GDP is not a specific inhibitor of UCP3, but also inhibits proton translocation by the adenine nucleotide translocase; and (iii) the inhibition of UCP3 by carboxyatractylate and bongkrekate is likely to be indirect, acting through the adenine nucleotide translocase.

scholarly journals AMP decreases the efficiency of skeletal-muscle mitochondria

2000 ◽  
Vol 351 (2) ◽  
pp. 307-311 ◽  
Author(s):  
Susana CADENAS ◽  
Julie A. BUCKINGHAM ◽  
Julie ST-PIERRE ◽  
Keith DICKINSON ◽  
Robert B. JONES ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Rate ◽  
Rana Temporaria ◽  
Adenine Nucleotide ◽  
Uncoupling Protein ◽  
Metabolic Efficiency ◽  
Proton Conductance ◽  
Muscle Mitochondria ◽  
Rat Muscle ◽  
Skeletal Muscle Mitochondria

Mitochondrial proton leak in rat muscle is responsible for approx. 15% of the standard metabolic rate, so its modulation could be important in regulating metabolic efficiency. We report in the present paper that physiological concentrations of AMP (K0.5 = 80µM) increase the resting respiration rate and double the proton conductance of rat skeletal-muscle mitochondria. This effect is specific for AMP. AMP also doubles proton conductance in skeletal-muscle mitochondria from an ectotherm (the frog Rana temporaria), suggesting that AMP activation is not primarily for thermogenesis. AMP activation in rat muscle mitochondria is unchanged when uncoupling protein-3 is doubled by starvation, indicating that this protein is not involved in the AMP effect. AMP activation is, however, abolished by inhibitors and substrates of the adenine nucleotide translocase (ANT), suggesting that this carrier (possibly the ANT1 isoform) mediates AMP activation. AMP activation of ANT could be important for physiological regulation of metabolic rate.

scholarly journals The Influence of Dietary Lipid Composition on Skeletal Muscle Mitochondria From Mice Following Eight Months of Calorie Restriction

2014 ◽  
pp. 57-71 ◽  
Author(s):  
Y. CHEN ◽  
K. HAGOPIAN ◽  
D. BIBUS ◽  
J. M. VILLALBA ◽  
G. LÓPEZ-LLUCH ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Calorie Restriction ◽  
Lipid Composition ◽  
Dietary Lipid ◽  
Complex Iii ◽  
Proton Leak ◽  
Phospholipid Fatty Acid Composition ◽  
Ros Production ◽  
Muscle Mitochondria

Calorie restriction (CR) has been shown to decrease reactive oxygen species (ROS) production and retard aging in a variety of species. It has been proposed that alterations in membrane saturation are central to these actions of CR. As a step towards testing this theory, mice were assigned to 4 dietary groups (control and 3 CR groups) and fed AIN-93G diets at 95 % (control) or 60 % (CR) of ad libitum for 8 months. To manipulate membrane composition, the primary dietary fats for the CR groups were soybean oil (also used in the control diet), fish oil or lard. Skeletal muscle mitochondrial lipid composition, proton leak, and H2O2 production were measured. Phospholipid fatty acid composition in CR mice was altered in a manner that reflected the n-3 and n-6 fatty acid profiles of their respective dietary lipid sources. Dietary lipid composition did not alter proton leak kinetics between the CR groups. However, the capacity of mitochondrial complex III to produce ROS was decreased in the CR lard compared to the other CR groups. The results of this study indicate that dietary lipid composition can influence ROS production in muscle mitochondria of CR mice. It remains to be determined if lard or other dietary oils can maximize the CR-induced decreases in ROS production.

Tissue variation of mitochondrial oxidative phosphorylation efficiency in cold-acclimated ducklings.

2010 ◽  
Vol 57 (4) ◽  
Author(s):  
Karine Salin ◽  
Loïc Teulier ◽  
Benjamin Rey ◽  
Jean-Louis Rouanet ◽  
Yann Voituron ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Cold Exposure ◽  
Gastrocnemius Muscle ◽  
Liver Mitochondria ◽  
Proton Leak ◽  
Proton Conductance ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Muscle Mitochondria ◽  
Important Contributor

We investigated the oxidative phosphorylation efficiency of liver and gastrocnemius muscle mitochondria in thermoneutral and cold-acclimated ducklings. The yield of oxidative phosphorylation was lower in muscle than in liver mitochondria, a difference that was associated with a higher proton conductance in muscle mitochondria. Cold exposure did not affect oxidative phosphorylation efficiency or basal proton leak in mitochondria. We conclude that the basal proton conductance of mitochondria may regulate mitochondrial oxidative phosphorylation efficiency, but is not an important contributor to thermogenic processes in cold-acclimated ducklings.

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

2010 ◽  
Vol 57 (4) ◽  
Author(s):  
Natalia P Komelina ◽  
Zarif G Amerkhanov
Keyword(s):  
Fatty Acid ◽  
Adenine Nucleotide ◽  
Uncoupling Protein ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Ground Squirrels ◽  
Adenine Nucleotide Translocase ◽  
Purine Nucleotides ◽  
Chloride Permeability ◽  
Brown Adipose

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.

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