Related Experiment Videos
AMP decreases the efficiency of skeletal-muscle mitochondria
S Cadenas1, J A Buckingham, J St-Pierre
1Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. sc@mrc-dunn.ca.ac.uk
Abstract:
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 (K(0.5)=80 microM) 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.
Insights
Adenosine monophosphate (AMP) significantly increases mitochondrial proton conductance in rat muscle, impacting metabolic rate. This AMP activation is mediated by the adenine nucleotide translocase (ANT), not uncoupling protein-3.
Area of Science:
- Mitochondrial physiology
- Metabolic regulation
- Cellular respiration
Background:
- Mitochondrial proton leak accounts for ~15% of standard metabolic rate.
- Modulating proton leak is key for regulating metabolic efficiency.
Purpose of the Study:
- To investigate the effect of adenosine monophosphate (AMP) on mitochondrial proton conductance in rat skeletal muscle.
- To determine the mechanism and physiological relevance of AMP-mediated changes in mitochondrial respiration.
Main Methods:
- Measuring resting respiration rate and proton conductance in isolated rat skeletal-muscle mitochondria.
- Testing the specificity of AMP effects and its impact on ectotherm mitochondria.
- Investigating the role of uncoupling protein-3 (UCP3) and adenine nucleotide translocase (ANT) in AMP activation.
Main Results:
- Physiological AMP concentrations (K(0.5)=80 microM) increase resting respiration and double proton conductance in rat skeletal-muscle mitochondria.
- AMP also doubles proton conductance in frog skeletal-muscle mitochondria, suggesting a non-thermogenic role.
- AMP activation is independent of UCP3 levels but is abolished by ANT inhibitors and substrates, implicating ANT (possibly ANT1) in the effect.
Conclusions:
- AMP is a potent activator of mitochondrial proton conductance in skeletal muscle.
- The adenine nucleotide translocase (ANT) likely mediates AMP activation of proton leak.
- AMP-mediated ANT activation may play a crucial role in the physiological regulation of metabolic rate.