Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Apr;78(4):2582–2586. doi: 10.1073/pnas.78.4.2582

Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol.

A J Waring, H Rottenberg, T Ohnishi, E Rubin
PMCID: PMC319393  PMID: 6264481

Abstract

Using the spin probe 5-doxylstearic acid, we studied the structural perturbations of rat liver mitochondrial membranes produced by exposure to ethanol in vitro and by chronic ethanol feeding. The addition of ethanol in vitro to mitochondria from control animals appears to "fluidize" the membranes, as evidenced by a pronounced decrease in the order parameter. By contrast, in membranes from rats fed ethanol chronically, there was no effect on the order parameter. This resistance of the mitochondrial membranes from chronically intoxicated animals to the fluidizing effect of ethanol probably results from a change in the composition of the phospholipids, because the same differential response to ethanol was observed upon using vesicles of mitochondrial phospholipids extracted from control and chronically treated rats. In the presence of 0.025--0.1 M ethanol, a range that prevails in the blood of chronic alcoholics, the order parameter of mitochondrial membranes from rats fed ethanol was comparable to that of control membranes without ethanol in vitro. Analysis of extracted mitochondrial phospholipids showed that the cardiolipin from ethanol-fed animals had fatty acyl residues that are more saturated than those of controls. These findings point to the underlying molecular mechanism of our previous observation that mitochondria from chronic alcoholic rats are more resistant to uncoupling by ethanol at physiological temperature [Rottenberg, H., Robertson, D. E. & Rubin, E. (1980) Lab. Invest. 42, 318--326]. We suggest that an adaptive change in the phospholipid composition leads to structural alterations, which result in increased resistance to disruption of mitochondrial membranes by ethanol. These changes in lipid composition and structure may explain many, if not all, of the mitochondrial abnormalities that have been previously reported to result from chronic ethanol intoxication.

Full text

PDF
2582

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. COURCHAINE A. J., MILLER W. H., STEIN D. B., Jr Rapid semi-micro procedure for estimating free and total cholesterol. Clin Chem. 1959 Dec;5:609–614. [PubMed] [Google Scholar]
  2. Cederbaum A. I., Lieber C. S., Rubin E. Effects of chronic ethanol treatment of mitochondrial functions damage to coupling site I. Arch Biochem Biophys. 1974 Dec;165(2):560–569. doi: 10.1016/0003-9861(74)90283-5. [DOI] [PubMed] [Google Scholar]
  3. Chin J. H., Goldstein D. B. Drug tolerance in biomembranes: a spin label study of the effects of ethanol. Science. 1977 May 6;196(4290):684–685. doi: 10.1126/science.193186. [DOI] [PubMed] [Google Scholar]
  4. Chin J. H., Goldstein D. B. Effects of low concentrations of ethanol on the fluidity of spin-labeled erythrocyte and brain membranes. Mol Pharmacol. 1977 May;13(3):435–441. [PubMed] [Google Scholar]
  5. Chin J. H., Parsons L. M., Goldstein D. B. Increased cholesterol content of erythrocyte and brain membranes in ethanol-tolerant mice. Biochim Biophys Acta. 1978 Nov 16;513(3):358–363. doi: 10.1016/0005-2736(78)90204-3. [DOI] [PubMed] [Google Scholar]
  6. Curran M., Seeman P. Alcohol tolerance in a cholinergic nerve terminal: relation to the membrane expansion-fluidization theory of ethanol action. Science. 1977 Aug 26;197(4306):910–911. doi: 10.1126/science.887931. [DOI] [PubMed] [Google Scholar]
  7. DeCarli L. M., Lieber C. S. Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate new liquid diet. J Nutr. 1967 Mar;91(3):331–336. doi: 10.1093/jn/91.3_Suppl.331. [DOI] [PubMed] [Google Scholar]
  8. Drachev L. A., Jasaitis A. A., Mikelsaar H., Nemecek I. B., Semenov A. Y., Semenova E. G., Severina I. I., Skulachev V. P. Reconstitution of biological molecular generators of electric current. H+-ATPase. J Biol Chem. 1976 Nov 25;251(22):7077–7082. [PubMed] [Google Scholar]
  9. French S. W., Ihrig T. J., Morin R. J. Lipid composition of RBC ghosts, liver mitochondria and microsomes of ethanol-fed rats. Q J Stud Alcohol. 1970 Dec;31(4):801–809. [PubMed] [Google Scholar]
  10. Gaffney B. J. Fatty acid chain flexibility in the membranes of normal and transformed fibroblasts. Proc Natl Acad Sci U S A. 1975 Feb;72(2):664–668. doi: 10.1073/pnas.72.2.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hill M. W., Bangham A. D. General depressant drug dependency : a biophysical hypothesis. Adv Exp Med Biol. 1975;59:1–9. doi: 10.1007/978-1-4757-0632-1_1. [DOI] [PubMed] [Google Scholar]
  12. Hubbell W. L., McConnell H. M. Molecular motion in spin-labeled phospholipids and membranes. J Am Chem Soc. 1971 Jan 27;93(2):314–326. doi: 10.1021/ja00731a005. [DOI] [PubMed] [Google Scholar]
  13. Johnson D. A., Lee N. M., Cooke R., Loh H. H. Ethanol-induced fluidization of brain lipid bilayers: required presence of cholesterol in membranes for the expression of tolerance. Mol Pharmacol. 1979 May;15(3):739–746. [PubMed] [Google Scholar]
  14. Keith A. D., Aloia R. C., Lyons J., Snipes W., Pengelley E. T. Spin label evidence for the role of lysoglycerophosphatides in cellular membranes of hibernating mammals. Biochim Biophys Acta. 1975 Jun 25;394(2):204–210. doi: 10.1016/0005-2736(75)90258-8. [DOI] [PubMed] [Google Scholar]
  15. Lee A. G. Interactions between anesthetics and lipid mixtures. Normal alcohols. Biochemistry. 1976 Jun 1;15(11):2448–2454. doi: 10.1021/bi00656a031. [DOI] [PubMed] [Google Scholar]
  16. Lundquist C. G., Kiessling K. H., Pilström L. Effect of ethanol on rat liver. 3. Lipid composition of liver mitochondria from rats after prolonged alcohol consumption. Acta Chem Scand. 1966;20(10):2751–2754. doi: 10.3891/acta.chem.scand.20-2751. [DOI] [PubMed] [Google Scholar]
  17. Mazzanti L., Curatola G., Zolese G., Bertoli E., Lenaz G. Lipid protein interactions in mitochondria. VIII. Effect of general anesthetics on the mobility of spin labels in lipid vesicles and mitochondrial membranes. J Bioenerg Biomembr. 1979 Apr;11(1-2):17–32. doi: 10.1007/BF00743158. [DOI] [PubMed] [Google Scholar]
  18. Miceli J. N., Ferrell W. J. Effects of ethanol on membrane lipids 3. Quantitative changes in lipid and fatty acid composition of nonpolar and polar lipids of mouse total liver, mitochondria and microsomes following ethanol feeding. Lipids. 1973 Dec;8(12):722–727. doi: 10.1007/BF02531839. [DOI] [PubMed] [Google Scholar]
  19. Paterson S. J., Butler K. W., Huang P., Labelle J., Smith I. C., Schneider H. The effects of alcohols on lipid bilayers: a spin label study. Biochim Biophys Acta. 1972 Jun 20;266(3):597–602. doi: 10.1016/0006-3002(72)90003-0. [DOI] [PubMed] [Google Scholar]
  20. Porta E. A., Hartroft W. S., De la Iglesia F. A. Hepatic changes associated with chronic alcoholism in rats. Lab Invest. 1965 Aug;14(8):1437–1455. [PubMed] [Google Scholar]
  21. Ragan C. I. The role of phospholipids in the reduction of ubiquinone analogues by the mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase complex. Biochem J. 1978 Jun 15;172(3):539–547. doi: 10.1042/bj1720539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roelofsen B., van Deenen L. L. Lipid requirement of membrane-bound ATPase. Studies on human erythrocyte ghosts. Eur J Biochem. 1973 Dec 3;40(1):245–257. doi: 10.1111/j.1432-1033.1973.tb03192.x. [DOI] [PubMed] [Google Scholar]
  23. Rottenberg H., Robertson D. E., Rubin E. The effect of ethanol on the temperature dependence of respiration and ATPase activities of rat liver mitochondria. Lab Invest. 1980 Mar;42(3):318–326. [PubMed] [Google Scholar]
  24. Seeman P. The membrane actions of anesthetics and tranquilizers. Pharmacol Rev. 1972 Dec;24(4):583–655. [PubMed] [Google Scholar]
  25. Thayer W. S., Rubin E. Effects of chronic ethanol intoxication on oxidative phosphorylation in rat liver submitochondrial particles. J Biol Chem. 1979 Aug 25;254(16):7717–7723. [PubMed] [Google Scholar]
  26. Thompson J. A., Reitz R. C. Effects of ethanol ingestion and dietary fat levels on mitochondrial lipids in male and female rats. Lipids. 1978 Aug;13(8):540–550. doi: 10.1007/BF02533593. [DOI] [PubMed] [Google Scholar]
  27. Trudell J. R., Hubbell W. L., Cohen E. N. The effect of two inhalation anesthetics on the order of spin-labeled phospholipid vesicles. Biochim Biophys Acta. 1973 Jan 26;291(2):321–327. doi: 10.1016/0005-2736(73)90485-9. [DOI] [PubMed] [Google Scholar]
  28. Vanderkooi G., Chazotte B., Biethman R. Temperature dependence of anesthetic effects on succinate oxidase activity in uncoupled submitochondrial particles. FEBS Lett. 1978 Jun 1;90(1):21–23. doi: 10.1016/0014-5793(78)80289-0. [DOI] [PubMed] [Google Scholar]
  29. Wuthier R. E. Purification of lipids from nonlipid contaminants on Sephadex bead columns. J Lipid Res. 1966 Jul;7(4):558–561. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES