title: AMP decreases the efficiency of skeletal-muscle mitochondria.
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.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. sc@mrc-dunn.ca.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Cadenas
authors.forename: J A
authors.initials: JA
authors.lastname: Buckingham
authors.forename: J
authors.initials: J
authors.lastname: St-Pierre
authors.forename: K
authors.initials: K
authors.lastname: Dickinson
authors.forename: R B
authors.initials: RB
authors.lastname: Jones
authors.forename: M D
authors.initials: MD
authors.lastname: Brand
mesh_terms: D000249:Adenosine Monophosphate / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D005508:Food Deprivation; D007473:Ion Channels; D007700:Kinetics; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption; D020033:Protein Isoforms; D011898:Ranidae; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D000071247:Uncoupling Protein 3
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D001278:Atractyloside; D000249:Adenosine Monophosphate; D000226:Mitochondrial ADP, ATP Translocases; C003853:carboxyatractyloside