Home LiteratureArticle Details
PMID: 11023814 Published · ppublish English Journal Article

AMP decreases the efficiency of skeletal-muscle mitochondria.

The Biochemical journal ·Vol. 351 Pt 2 ·2000-10-15 ·Pages 307-11

Cadenas S, Buckingham JA, St-Pierre J, Dickinson K, Jones RB, Brand MD

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.

MeSH Terms
Adenosine Monophosphate/pharmacology,physiology Animals Atractyloside/analogs & derivatives,metabolism Carrier Proteins/metabolism Dose-Response Relationship, Drug Electrophysiology Female Food Deprivation Ion Channels Kinetics Membrane Potentials Mitochondria/metabolism Mitochondria, Liver/metabolism Mitochondrial ADP, ATP Translocases/metabolism Mitochondrial Proteins Muscle, Skeletal/metabolism Oxygen Consumption Protein Isoforms Ranidae Rats Rats, Wistar Temperature Uncoupling Protein 3
Chemicals
Carrier Proteins Ion Channels Mitochondrial Proteins Protein Isoforms Ucp3 protein, rat Uncoupling Protein 3 Atractyloside Adenosine Monophosphate Mitochondrial ADP, ATP Translocases carboxyatractyloside
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cadenas S
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. sc@mrc-dunn.ca.ac.uk
Buckingham J A
St-Pierre J
Dickinson K
Jones R B
Brand M D
References (34)
34 references, click to expand
  1. UCP2 and UCP3 rise in starved rat skeletal muscle but mitochondrial proton conductance is unchanged.
    FEBS Lett. 1999 Dec 3;462(3):257-60 PMID: 10622707
  2. Biochemical and osmotic properties of skeletal muscle mitochondria.
    Nature. 1954 Jun 5;173(4414):1094-5 PMID: 13165721
  3. Effects of magnesium and nucleotides on the proton conductance of rat skeletal-muscle mitochondria.
    Biochem J. 2000 May 15;348 Pt 1:209-13 PMID: 10794733
  4. [Mitochondria from brown adipose tissue: uncoupling of respiratory chain phosphorylation by long fatty acids and recoupling by guanosine triphosphate].
    Hoppe Seylers Z Physiol Chem. 1969 Sep;350(9):1121-31 PMID: 5388738
  5. The influence of respiration and ATP hydrolysis on the proton-electrochemical gradient across the inner membrane of rat-liver mitochondria as determined by ion distribution.
    Eur J Biochem. 1974 Dec 16;50(1):305-15 PMID: 4452361
  6. Molecular and physiological aspects of adenine nucleotide transport in mitochondria.
    Biochim Biophys Acta. 1976 Apr 30;456(1):1-38 PMID: 131583
  7. The effective proton conductance of the inner membrane of mitochondria from brown adipose tissue. Dependency on proton electrochemical potential gradient.
    Eur J Biochem. 1977 Jul 15;77(2):349-56 PMID: 19250
  8. Thermogenic mechanisms in brown fat.
    Physiol Rev. 1984 Jan;64(1):1-64 PMID: 6320232
  9. O2 solubility in aqueous media determined by a kinetic method.
    Anal Biochem. 1985 Mar;145(2):406-18 PMID: 4014672
  10. Effect of warm or cold exposure on GDP binding and uncoupling protein in rat brown fat.
    Am J Physiol. 1987 Feb;252(2 Pt 1):E237-43 PMID: 3826341
  11. Adenine nucleotide transport and adenosine production in isolated rat heart mitochondria during acetate metabolism.
    Biochim Biophys Acta. 1989 May 30;974(3):274-81 PMID: 2543456
  12. The proton leak across the mitochondrial inner membrane.
    Biochim Biophys Acta. 1990 Jul 25;1018(2-3):128-33 PMID: 2393654
  13. Isolation of skeletal muscle mitochondria from hamsters using an ionic medium containing ethylenediaminetetraacetic acid and nagarse.
    Anal Biochem. 1991 Feb 1;192(2):344-9 PMID: 1903610
  14. Interaction of adenine nucleotides with the adenine nucleotide translocase regulates the developmental changes in proton conductance of the inner mitochondrial membrane.
    FEBS Lett. 1991 Dec 9;294(3):225-8 PMID: 1661684
  15. Control of oxidative phosphorylation in rat muscle mitochondria: implications for mitochondrial myopathies.
    Biochim Biophys Acta. 1993 Feb 8;1141(1):58-64 PMID: 8382080
  16. Purine nucleoside formation in rat skeletal muscle fiber types.
    Am J Physiol. 1993 May;264(5 Pt 1):C1246-51 PMID: 8498484
  17. The causes and functions of mitochondrial proton leak.
    Biochim Biophys Acta. 1994 Aug 30;1187(2):132-9 PMID: 8075107
  18. Characteristics of mitochondrial proton leak and control of oxidative phosphorylation in the major oxygen-consuming tissues of the rat.
    Biochim Biophys Acta. 1994 Dec 30;1188(3):405-16 PMID: 7803454
  19. Fluorescent nucleotide derivatives as specific probes for the uncoupling protein: thermodynamics and kinetics of binding and the control by pH.
    Biochemistry. 1995 Jan 10;34(1):349-60 PMID: 7819218
  20. The nature and regulation of the ATP-induced anion permeability in Saccharomyces cerevisiae mitochondria.
    Arch Biochem Biophys. 1996 Oct 1;334(1):43-9 PMID: 8837737
  21. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia.
    Nat Genet. 1997 Mar;15(3):269-72 PMID: 9054939
  22. Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis.
    Diabetes. 1997 May;46(5):900-6 PMID: 9133562
  23. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression.
    FEBS Lett. 1997 May 12;408(1):39-42 PMID: 9180264
  24. The pH-dependent reciprocal changes in contributions of ADP/ATP antiporter and aspartate/glutamate antiporter to the fatty acid-induced uncoupling.
    FEBS Lett. 1997 Jul 21;412(1):179-82 PMID: 9257716
  25. A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation.
    FASEB J. 1997 Aug;11(10):809-15 PMID: 9271366
  26. Uncoupling: new approaches to an old problem of bioenergetics.
    Biochim Biophys Acta. 1998 Feb 25;1363(2):100-24 PMID: 9507078
  27. Top-down elasticity analysis and its application to energy metabolism in isolated mitochondria and intact cells.
    Mol Cell Biochem. 1998 Jul;184(1-2):13-20 PMID: 9746309
  28. Binding of nucleotides by the mitochondrial ADP/ATP carrier as studied by 1H nuclear magnetic resonance spectroscopy.
    Biochemistry. 1999 Jan 12;38(2):762-9 PMID: 9888816
  29. Contribution of mitochondrial proton leak to respiration rate in working skeletal muscle and liver and to SMR.
    Am J Physiol. 1999 Mar;276(3 Pt 1):C692-9 PMID: 10069997
  30. Transcription of the adenine nucleotide translocase isoforms in various types of tissues in the rat.
    Biochim Biophys Acta. 1999 Feb 4;1417(1):16-24 PMID: 10076031
  31. Regulation of UCP3 by nucleotides is different from regulation of UCP1.
    FEBS Lett. 1999 Apr 30;450(1-2):8-12 PMID: 10350047
  32. UCP1, UCP2 and UCP3: are they true uncouplers of respiration?
    Int J Obes Relat Metab Disord. 1999 Jun;23 Suppl 6:S19-23 PMID: 10454116
  33. Transport function and regulation of mitochondrial uncoupling proteins 2 and 3.
    J Biol Chem. 1999 Sep 10;274(37):26003-7 PMID: 10473545
  34. Mitochondrial proton leak and the uncoupling proteins.
    J Bioenerg Biomembr. 1999 Oct;31(5):517-25 PMID: 10653479
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
Email
sc@mrc-dunn.ca.ac.uk
Published
2000-10-15
Pages
307-11
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1221364
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2