|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 275, Issue 1, 223-228, January 7, 2000
From the Laboratoire de Bioénergétique Fondamentale et
Appliquée, Université Joseph Fourier, F-38041
Grenoble-Cedex 09, France and § the Institut de Biochimie et
de Génétique Cellulaires du CNRS, Université de
Bordeaux II, F-33077 Bordeaux-Cedex, France
We report here a new mitochondrial regulation
occurring only in intact cells. We have investigated the effects of
dimethylbiguanide on isolated rat hepatocytes, permeabilized
hepatocytes, and isolated liver mitochondria. Addition of
dimethylbiguanide decreased oxygen consumption and mitochondrial
membrane potential only in intact cells but not in permeabilized
hepatocytes or isolated mitochondria. Permeabilized hepatocytes after
dimethylbiguanide exposure and mitochondria isolated from
dimethylbiguanide pretreated livers or animals were characterized by a
significant inhibition of oxygen consumption with complex I substrates
(glutamate and malate) but not with complex II (succinate) or complex
IV
(N,N,N',N'-tetramethyl-1,4-phenylenediamine dihydrochloride (TMPD)/ascorbate) substrates. Studies using
functionally isolated complex I obtained from mitochondria isolated
from dimethylbiguanide-pretreated livers or rats further confirmed that
dimethylbiguanide action was located on the respiratory chain complex
I. The dimethylbiguanide effect was temperature-dependent,
oxygen consumption decreasing by 50, 20, and 0% at 37, 25, and
15 °C, respectively. This effect was not affected by
insulin-signaling pathway inhibitors, nitric oxide precursor or
inhibitors, oxygen radical scavengers, ceramide synthesis inhibitors,
or chelation of intra- or extracellular Ca2+. Because it is
established that dimethylbiguanide is not metabolized, these results
suggest the existence of a new cell-signaling pathway targeted to the
respiratory chain complex I with a persistent effect after cessation of
the signaling process.
Dimethylbiguanide Inhibits Cell Respiration via an Indirect
Effect Targeted on the Respiratory Chain Complex I*
,
*
This work was supported by the Grant EP000983-01 from the
Fondation pour la Recherche Médicale, France (to M.-Y. El-Mir) and by the Ministère de l'Enseignement, de la Recherche et de la
Technologie.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
On leave from the Departamento de Fisiologia y Farmacologia,
Facultad de Farmacia, Universidad de Salamanca-E-37007, Spain.
¶
To whom correspondence should be addressed: Laboratoire de
Bioénergétique Fondamentale et Appliquée,
Université Joseph Fourier, B. P. 53X, F-38041 Grenoble-Cedex 09, France. Fax: 33-4-76-51-42-18; E-mail:
xavier.leverve@ujf-grenoble.fr.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. R. Steinberg and B. E. Kemp AMPK in Health and Disease Physiol Rev, July 1, 2009; 89(3): 1025 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. T.F. Facundo and S. P. Jones AMP-Dependent Protein Kinase Activators: Not Just for Diabetes? Circ. Res., February 13, 2009; 104(3): 282 - 284. [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Richardson, S. Ingamells, C. D. Simonis, I. T. Cameron, R. Sreekumar, A. Vijendren, L. Sellahewa, S. Coakley, and C. D. Byrne Stimulation of Lactate Production in Human Granulosa Cells by Metformin and Potential Involvement of Adenosine 5' Monophosphate-Activated Protein Kinase J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 670 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K Nyblom, E. Sargsyan, and P. Bergsten AMP-activated protein kinase agonist dose dependently improves function and reduces apoptosis in glucotoxic {beta}-cells without changing triglyceride levels J. Mol. Endocrinol., September 1, 2008; 41(3): 187 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Zmijewski, E. Lorne, X. Zhao, Y. Tsuruta, Y. Sha, G. Liu, G. P. Siegal, and E. Abraham Mitochondrial Respiratory Complex I Regulates Neutrophil Activation and Severity of Lung Injury Am. J. Respir. Crit. Care Med., July 15, 2008; 178(2): 168 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Turner, J.-Y. Li, A. Gosby, S. W.C. To, Z. Cheng, H. Miyoshi, M. M. Taketo, G. J. Cooney, E. W. Kraegen, D. E. James, et al. Berberine and Its More Biologically Available Derivative, Dihydroberberine, Inhibit Mitochondrial Respiratory Complex I: A Mechanism for the Action of Berberine to Activate AMP-Activated Protein Kinase and Improve Insulin Action Diabetes, May 1, 2008; 57(5): 1414 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Mukhtar, V. A. Payne, C. Arden, A. Harbottle, S. Khan, A. J. Lange, and L. Agius Inhibition of glucokinase translocation by AMP-activated protein kinase is associated with phosphorylation of both GKRP and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R766 - R774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Xie, Y. Dong, R. Scholz, D. Neumann, and M.-H. Zou Phosphorylation of LKB1 at Serine 428 by Protein Kinase C-{zeta} Is Required for Metformin-Enhanced Activation of the AMP-Activated Protein Kinase in Endothelial Cells Circulation, February 19, 2008; 117(7): 952 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Goransson, A. McBride, S. A. Hawley, F. A. Ross, N. Shpiro, M. Foretz, B. Viollet, D. G. Hardie, and K. Sakamoto Mechanism of Action of A-769662, a Valuable Tool for Activation of AMP-activated Protein Kinase J. Biol. Chem., November 9, 2007; 282(45): 32549 - 32560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Buzzai, R. G. Jones, R. K. Amaravadi, J. J. Lum, R. J. DeBerardinis, F. Zhao, B. Viollet, and C. B. Thompson Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficient Tumor Cell Growth Cancer Res., July 15, 2007; 67(14): 6745 - 6752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Kramer, L. Al-Khalili, B. Guigas, Y. Leng, P. M. Garcia-Roves, and A. Krook Role of AMP Kinase and PPAR{delta} in the Regulation of Lipid and Glucose Metabolism in Human Skeletal Muscle J. Biol. Chem., July 6, 2007; 282(27): 19313 - 19320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhang, H. He, and J. A. Balschi Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H457 - H466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kaminski, M. Kiessling, D. Suss, P. H. Krammer, and K. Gulow Novel Role for Mitochondria: Protein Kinase C{theta}-Dependent Oxidative Signaling Organelles in Activation-Induced T-Cell Death Mol. Cell. Biol., May 15, 2007; 27(10): 3625 - 3639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Jacobs, S. Lingrell, J. R. B. Dyck, and D. E. Vance Inhibition of Hepatic Phosphatidylcholine Synthesis by 5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside Is Independent of AMP-activated Protein Kinase Activation J. Biol. Chem., February 16, 2007; 282(7): 4516 - 4523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Towler and D. G. Hardie AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling Circ. Res., February 16, 2007; 100(3): 328 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Hardie, S. A. Hawley, and J. W. Scott AMP-activated protein kinase - development of the energy sensor concept J. Physiol., July 1, 2006; 574(1): 7 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Evans AMP-activated protein kinase and the regulation of Ca2+ signalling in O2-sensing cells J. Physiol., July 1, 2006; 574(1): 113 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bertrand, A. Ginion, C. Beauloye, A. D. Hebert, B. Guigas, L. Hue, and J.-L. Vanoverschelde AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H239 - H250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Guigas, L. Bertrand, N. Taleux, M. Foretz, N. Wiernsperger, D. Vertommen, F. Andreelli, B. Viollet, and L. Hue 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside and Metformin Inhibit Hepatic Glucose Phosphorylation by an AMP-Activated Protein Kinase-Independent Effect on Glucokinase Translocation. Diabetes, April 1, 2006; 55(4): 865 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Hardie and K. Sakamoto AMPK: A Key Sensor of Fuel and Energy Status in Skeletal Muscle Physiology, February 1, 2006; 21(1): 48 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Evans, K. J. W. Mustard, C. N. Wyatt, C. Peers, M. Dipp, P. Kumar, N. P. Kinnear, and D. G. Hardie Does AMP-activated Protein Kinase Couple Inhibition of Mitochondrial Oxidative Phosphorylation by Hypoxia to Calcium Signaling in O2-sensing Cells? J. Biol. Chem., December 16, 2005; 280(50): 41504 - 41511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M Woollhead, J. W Scott, D. G. Hardie, and D. L Baines Phenformin and 5-aminoimidazole-4-carboxamide-1-{beta}-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells J. Physiol., August 1, 2005; 566(3): 781 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Detaille, B. Guigas, C. Chauvin, C. Batandier, E. Fontaine, N. Wiernsperger, and X. Leverve Metformin Prevents High-Glucose-Induced Endothelial Cell Death Through a Mitochondrial Permeability Transition-Dependent Process Diabetes, July 1, 2005; 54(7): 2179 - 2187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Marchetti, S. Del Guerra, L. Marselli, R. Lupi, M. Masini, M. Pollera, M. Bugliani, U. Boggi, F. Vistoli, F. Mosca, et al. Pancreatic Islets from Type 2 Diabetic Patients Have Functional Defects and Increased Apoptosis That Are Ameliorated by Metformin J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5535 - 5541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Zou, S. S. Kirkpatrick, B. J. Davis, J. S. Nelson, W. G. Wiles IV, U. Schlattner, D. Neumann, M. Brownlee, M. B. Freeman, and M. H. Goldman Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo: ROLE OF MITOCHONDRIAL REACTIVE NITROGEN SPECIES J. Biol. Chem., October 15, 2004; 279(42): 43940 - 43951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Brunmair, A. Lest, K. Staniek, F. Gras, N. Scharf, M. Roden, H. Nohl, W. Waldhausl, and C. Furnsinn Fenofibrate Impairs Rat Mitochondrial Function by Inhibition of Respiratory Complex I J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 109 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Brunmair, K. Staniek, F. Gras, N. Scharf, A. Althaym, R. Clara, M. Roden, E. Gnaiger, H. Nohl, W. Waldhausl, et al. Thiazolidinediones, Like Metformin, Inhibit Respiratory Complex I: A Common Mechanism Contributing to Their Antidiabetic Actions? Diabetes, April 1, 2004; 53(4): 1052 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-S. Wang, H. Kusuhara, Y. Kato, J. W. Jonker, A. H. Schinkel, and Y. Sugiyama Involvement of Organic Cation Transporter 1 in the Lactic Acidosis Caused by Metformin Mol. Pharmacol., April 1, 2003; 63(4): 844 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Gunton, P. J. D. Delhanty, S.-I. Takahashi, and R. C. Baxter Metformin Rapidly Increases Insulin Receptor Activation in Human Liver and Signals Preferentially through Insulin-Receptor Substrate-2 J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1323 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-S. Wang, J. W. Jonker, Y. Kato, H. Kusuhara, A. H. Schinkel, and Y. Sugiyama Involvement of Organic Cation Transporter 1 in Hepatic and Intestinal Distribution of Metformin J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 510 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Musi, M. F. Hirshman, J. Nygren, M. Svanfeldt, P. Bavenholm, O. Rooyackers, G. Zhou, J. M. Williamson, O. Ljunqvist, S. Efendic, et al. Metformin Increases AMP-Activated Protein Kinase Activity in Skeletal Muscle of Subjects With Type 2 Diabetes Diabetes, July 1, 2002; 51(7): 2074 - 2081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Arlt, R. J. Auchus, and W. L. Miller Thiazolidinediones but Not Metformin Directly Inhibit the Steroidogenic Enzymes P450c17 and 3beta -Hydroxysteroid Dehydrogenase J. Biol. Chem., May 11, 2001; 276(20): 16767 - 16771. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |