Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate

1996 ◽  
Vol 271 (4) ◽  
pp. C1380-C1389 ◽  
Author(s):  
D. F. Rolfe ◽  
M. D. Brand
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Rate ◽  
Respiration Rate ◽  
Rat Hepatocytes ◽  
Standard Metabolic Rate ◽  
Proton Leak ◽  
Rat Skeletal Muscle ◽  
Isolated Rat Hepatocytes ◽  
Mitochondrial Inner Membrane

We have tested the hypothesis that the leak of protons across the mitochondrial inner membrane (proton leak) is a significant contributor to standard metabolic rate (SMR). We found that proton leak accounts for around one-half of the resting respiration rate of perfused rat skeletal muscle. Proton leak is known to make a significant (26%) contribution to the resting respiration rate of isolated rat hepatocytes (M. D. Brand, L.-F. Chien, E. K. Ainscow, D. F. S. Rolfe, and R. K. Porter. Biochim. Biophys. Acta 1187: 132-139, 1994). If the importance of proton leak in these isolated and perfused systems is similar to its importance in vivo, then using literature values for the contribution of liver and skeletal muscle to SMR, we can calculate that proton leak in liver and skeletal muscle alone accounts for 11-26% (mean 20%) of the SMR of the rat. If proton leak activity in the other tissues of the rat is similar to that in liver cells, then the contribution of proton leak to rat SMR would be 16-31% (mean 25%).

Contribution of mitochondrial proton leak to respiration rate in working skeletal muscle and liver and to SMR

1999 ◽  
Vol 276 (3) ◽  
pp. C692-C699 ◽  
Author(s):  
David F. S. Rolfe ◽  
John M. B. Newman ◽  
Julie A. Buckingham ◽  
Michael G. Clark ◽  
Martin D. Brand
Keyword(s):  
Skeletal Muscle ◽  
Respiration Rate ◽  
Rat Hepatocytes ◽  
Standard Metabolic Rate ◽  
Proton Pumping ◽  
High Rate ◽  
Proton Leak ◽  
Futile Cycle

Proton pumping across the mitochondrial inner membrane and proton leak back through the natural proton conductance pathway make up a futile cycle that dissipates redox energy. We measured respiration and average mitochondrial membrane potential in perfused rat hindquarter with maximal tetanic contraction of the left gastrocnemius-soleus-plantaris muscle group, and we estimate that the mitochondrial proton cycle accounted for 34% of the respiration rate of the preparation. Similar measurements in rat hepatocytes given substrates to cause a high rate of gluconeogenesis and ureagenesis showed that the proton cycle accounted for 22% of the respiration rate of these cells. Combining these in vitro values with literature values for the contribution of skeletal muscle and liver to standard metabolic rate (SMR), we calculate that the proton cycle in working muscle and liver may account for 15% of SMR in vivo. Although this value is less than the 20% of SMR we calculated previously using data from resting skeletal muscle and hepatocytes, it is still large, and we conclude that the futile proton cycle is a major contributor to SMR.

scholarly journals Evolution of energy metabolism. Proton permeability of the inner membrane of liver mitochondria is greater in a mammal than in a reptile

1991 ◽  
Vol 275 (1) ◽  
pp. 81-86 ◽  
Author(s):  
M D Brand ◽  
P Couture ◽  
P L Else ◽  
K W Withers ◽  
A J Hulbert
Keyword(s):  
Metabolic Rate ◽  
Mitochondrial Membrane ◽  
Mitochondrial Protein ◽  
Rat Hepatocytes ◽  
Liver Mitochondria ◽  
Standard Metabolic Rate ◽  
Proton Permeability ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Bearded Dragon

Standard metabolic rate is 7-fold greater in the rat (a typical mammal) than in the bearded dragon, Amphibolurus vitticeps (a reptile with the same body mass and temperature). Rat hepatocytes respire 4-fold faster than do hepatocytes from the lizard. The inner membrane of isolated rat liver mitochondrial has a proton permeability that is 4-5-fold greater than the proton permeability of the lizard liver mitochondrial membrane per mg of mitochondrial protein. The greater permeability of rat mitochondria is not caused by differences in the surface area of the mitochondrial inner membrane, but differences in the fatty acid composition of the mitochondrial phospholipids may be involved in the permeability differences. Greater proton permeability of the mitochondrial inner membrane may contribute to the greater standard metabolic rate of mammals.

Proton leak induced by reactive oxygen species produced during in vitro anoxia/reoxygenation in rat skeletal muscle mitochondria

2006 ◽  
Vol 38 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Rachel Navet ◽  
Ange Mouithys-Mickalad ◽  
Pierre Douette ◽  
Claudine M. Sluse-Goffart ◽  
Wieslawa Jarmuszkiewicz ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Reactive Oxygen ◽  
Proton Leak ◽  
Oxygen Species ◽  
Rat Skeletal Muscle ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria

Regulation of glucose transporter GLUT-4 and hexokinase II gene transcription by insulin and epinephrine

1997 ◽  
Vol 273 (4) ◽  
pp. E682-E687 ◽  
Author(s):  
Jared P. Jones ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Gene Transcription ◽  
Glucose Transporter ◽  
Male Rats ◽  
Rat Skeletal Muscle ◽  
Hexokinase Ii ◽  
Epinephrine Infusion ◽  
Glut 4 ◽  
Gastrocnemius Muscles

Transport of glucose across the plasma membrane by GLUT-4 and subsequent phosphorylation of glucose by hexokinase II (HKII) constitute the first two steps of glucose utilization in skeletal muscle. This study was undertaken to determine whether epinephrine and/or insulin regulates in vivo GLUT-4 and HKII gene transcription in rat skeletal muscle. In the first experiment, adrenodemedullated male rats were fasted 24 h and killed in the control condition or after being infused for 1.5 h with epinephrine (30 μg/ml at 1.68 ml/h). In the second experiment, male rats were fasted 24 h and killed after being infused for 2.5 h at 1.68 ml/h with saline or glucose (625 mg/ml) or insulin (39.9 μg/ml) plus glucose (625 mg/ml). Nuclei were isolated from pooled quadriceps, tibialis anterior, and gastrocnemius muscles. Transcriptional run-on analysis indicated that epinephrine infusion decreased GLUT-4 and increased HKII transcription compared with fasted controls. Both glucose and insulin plus glucose infusion induced increases in GLUT-4 and HKII transcription of twofold and three- to fourfold, respectively, compared with saline-infused rats. In conclusion, epinephrine and insulin may regulate GLUT-4 and HKII genes at the level of transcription in rat skeletal muscle.

scholarly journals Comparative metabolism of the antiviral dimer 3'-azido-3'-deoxythymidine-P-2',3'-dideoxyinosine and the monomers zidovudine and didanosine by rat, monkey, and human hepatocytes.

1997 ◽  
Vol 41 (11) ◽  
pp. 2502-2510 ◽  
Author(s):  
X R Pan-Zhou ◽  
E Cretton-Scott ◽  
X J Zhou ◽  
M Y Xie ◽  
R Rahmani ◽  
...  
Keyword(s):  
High Performance ◽  
Rat Hepatocytes ◽  
Human Hepatocytes ◽  
Metabolic Fate ◽  
Extracellular Medium ◽  
Isolated Rat Hepatocytes ◽  
Cell Extracts ◽  
Comparative Metabolism ◽  
Isolated Rat

AZT-P-ddI is an antiviral heterodimer composed of one molecule of 3'-azido-3'-deoxythymidine (AZT) and one molecule of 2',3'-dideoxyinosine (ddI) linked through their 5' positions by a phosphate bond. The metabolic fate of the dimer was studied with isolated rat, monkey, and human hepatocytes and was compared with that of its component monomers AZT and ddI. Upon incubation of double-labeled [14C]AZT-P-[3H]ddI in freshly isolated rat hepatocytes in suspension at a final concentration of 10 microM, the dimer was taken up intact by cells and then rapidly cleaved to AZT, AZT monophosphate, ddI, and ddI monophosphate. AZT and ddI so formed were then subject to their respective catabolisms. High-performance liquid chromatography analyses of the extracellular medium and cell extracts revealed the presence of unchanged dimer, AZT, 3'-azido-3'-deoxy-5'-beta-D-glucopyranosylthymidine (GAZT), 3'-amino-3'-deoxythymidine (AMT), ddI, and a previously unrecognized derivative of the dideoxyribose moiety of ddI, designated ddI-M. Trace extracellular but substantial intracellular levels of the glucuronide derivative of AMT (3'-amino-3'-deoxy-5'-beta-D-glucopyranosylthymidine [GAMT]) were also detected. Moreover, the extent of the formation of AMT, GAZT, and ddI-M from the dimer was markedly lower than that with AZT and ddI alone by the hepatocytes. With hepatocytes in primary culture obtained from rat, monkey, and human, large interspecies variations in the metabolism of AZT-P-ddI were observed. While GAZT and ddI-M, metabolites of AZT and ddI, respectively, as well as AZT 5'-monophosphate (MP) and ddI-MP were detected in the extracellular media of all species, AMT and GAMT were produced only by rat and monkey hepatocytes. No such metabolites were formed by human hepatocytes. The metabolic fate of the dimer by human hepatocytes was consistent with in vivo data recently obtained from human immunodeficiency virus-infected patients.

Trophic effect of iron-bound transferrin on acetylcholine receptors in rat skeletal muscle in vivo

1983 ◽  
Vol 38 (3) ◽  
pp. 303-307 ◽  
Author(s):  
Keiji Wada ◽  
Satoshi Ueno ◽  
Takanori Hazama ◽  
Hiro-O Yoshikawa ◽  
Saburo Ogasahara ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Acetylcholine Receptors ◽  
Rat Skeletal Muscle ◽  
Trophic Effect

Stable incorporation of a bacterial gene into adult rat skeletal muscle in vivo

1990 ◽  
Vol 258 (3) ◽  
pp. C578-C581 ◽  
Author(s):  
D. B. Thomason ◽  
F. W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Leukemia Virus ◽  
Rat Skeletal Muscle ◽  
Bacterial Gene ◽  
Muscle Gene Expression ◽  
Adult Rat ◽  
Foreign Genes ◽  
Muscle Gene ◽  
Beta Galactosidase

We have developed a novel technique to incorporate and stably express foreign genes in adult rat skeletal muscle in vivo. Endogeneous satellite cells in skeletal muscle regenerating from bupivacaine damage were infected with an injected retrovirus containing the Escherichia coli beta-galactosidase gene under the promoter control of the Moloney murine leukemia virus long-terminal repeat. Constitutive and stable expression of beta-galactosidase activity was observed in muscle fibers after 6 days and 1 mo of muscle regeneration. Two patterns of expression were observed, diffuse expression within fibers and focal expression associated with the sarcolemma. This technique will allow future experiments with muscle-specific genes and promoters to study the physiological regulation of skeletal muscle gene expression in the intact adult mammal. Furthermore, the technique of stimulating stem cell proliferation to allow retroviral-mediated gene transfer may be generally applicable to other tissues.

scholarly journals Histological examinations of the in vivo biocompatibility of oxycellulose implanted into rat skeletal muscle

2018 ◽  
Vol 28 (5) ◽  
pp. 593-599
Author(s):  
Christiane Kunert-Keil ◽  
Isabel Narath ◽  
Jakub Hadzik ◽  
Tomasz Gedrange ◽  
Tomasz Gredes ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Rat Skeletal Muscle
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