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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
. 1988 May;85(10):3353–3357. doi: 10.1073/pnas.85.10.3353

Cardiolipin from ethanol-fed rats confers tolerance to ethanol in liver mitochondrial membranes.

J S Ellingson 1, T F Taraschi 1, A Wu 1, R Zimmerman 1, E Rubin 1
PMCID: PMC280207  PMID: 3368447

Abstract

In rats chronically consuming ethanol, the liver mitochondrial membranes develop resistance to the disordering effects of ethanol in vitro, so-called "membrane tolerance". To investigate the molecular basis of this tolerance in the inner mitochondrial membrane, multilamellar vesicles were produced by recombining the mitoplast phospholipids (quantitatively separated by preparative HPLC) from control and ethanol-fed animals in various combinations. The effect of in vitro ethanol on the physical properties of these vesicles was determined by electron spin resonance. Vesicles composed of all mitoplast phospholipids from control rats were disordered by 50-100 mM ethanol, whereas those made of the phospholipids from ethanol-fed animals were resistant. When phosphatidylcholine (46 mol %) or phosphatidylethanolamine (42 mol %) from ethanol-fed rats replaced the corresponding phospholipids of control rats, the vesicles were disordered by ethanol. By contrast, when as little as 2.5 mol % of cardiolipin (one-fourth the naturally occurring amount) from ethanol-fed rats replaced that phospholipid from control rats, vesicles were rendered entirely resistant to disordering by ethanol. The same amount of cardiolipin from ethanol-fed rats also conferred membrane tolerance to vesicles composed of bovine phospholipids, demonstrating that this effect is not restricted to rat mitoplast phospholipids. In vesicles composed of a single mitoplast-phospholipid class, only vesicles composed of cardiolipin from ethanol-fed rats resisted disordering. Phosphatidylinositol from liver microsomes of ethanol-fed rats also confers membrane tolerance and was the only microsomal phospholipid that formed tolerant vesicles. Thus, in livers of rats chronically fed ethanol, anionic phospholipids are selectively converted into potent promoters of membrane tolerance in both mitochondrial and microsomal membranes.

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Selected References

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  1. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Cederbaum A. I., Lieber C. S., Toth A., Beattie D. S., Rubin E. Effects of ethanol and fat on the transport of reducing equivalents into rat liver mitochondria. J Biol Chem. 1973 Jul 25;248(14):4977–4986. [PubMed] [Google Scholar]
  4. 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]
  5. Cunningham C. C., Spach P. I. The effect of chronic ethanol consumption on the lipids in liver mitochondria. Ann N Y Acad Sci. 1987;492:181–192. doi: 10.1111/j.1749-6632.1987.tb48667.x. [DOI] [PubMed] [Google Scholar]
  6. Daum G. Lipids of mitochondria. Biochim Biophys Acta. 1985 Jun 12;822(1):1–42. doi: 10.1016/0304-4157(85)90002-4. [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. Demiel R. A., Guerts van Kessel W. S., van Deenen L. L. The properties of polyunsaturated lecithins in monolayers and liposomes and the interactions of these lecithins with cholesterol. Biochim Biophys Acta. 1972 Apr 14;266(1):26–40. doi: 10.1016/0005-2736(72)90116-2. [DOI] [PubMed] [Google Scholar]
  9. Ellingson J. S. Changes in the phospholipid composition in the differentiating cellular slime mold, Dictyostelium discoideum. Biochim Biophys Acta. 1974 Jan 23;337(1):60–67. doi: 10.1016/0005-2760(74)90040-x. [DOI] [PubMed] [Google Scholar]
  10. Ellingson J. S., Zimmerman R. L. Rapid separation of gram quantities of phospholipids from biological membranes by preparative high performance liquid chromatography. J Lipid Res. 1987 Aug;28(8):1016–1018. [PubMed] [Google Scholar]
  11. 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]
  12. LIEBER C. S., JONES D. P., DECARLI L. M. EFFECTS OF PROLONGED ETHANOL INTAKE: PRODUCTION OF FATTY LIVER DESPITE ADEQUATE DIETS. J Clin Invest. 1965 Jun;44:1009–1021. doi: 10.1172/JCI105200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. MORRISON W. R., SMITH L. M. PREPARATION OF FATTY ACID METHYL ESTERS AND DIMETHYLACETALS FROM LIPIDS WITH BORON FLUORIDE--METHANOL. J Lipid Res. 1964 Oct;5:600–608. [PubMed] [Google Scholar]
  14. Ponnappa B. C., Hoek J. B., Waring A. J., Rubin E. Effect of ethanol on amylase secretion and cellular calcium homeostasis in pancreatic acini from normal and ethanol-fed rats. Biochem Pharmacol. 1987 Jan 1;36(1):69–79. doi: 10.1016/0006-2952(87)90383-2. [DOI] [PubMed] [Google Scholar]
  15. Rubin E., Lieber C. S. Alcohol-induced hepatic injury in nonalcoholic volunteers. N Engl J Med. 1968 Apr 18;278(16):869–876. doi: 10.1056/NEJM196804182781602. [DOI] [PubMed] [Google Scholar]
  16. Rubin E., Lieber C. S. Early fine structural changes in the human liver induced by alcohol. Gastroenterology. 1967 Jan;52(1):1–13. [PubMed] [Google Scholar]
  17. Rubin E., Lieber C. S. Experimental alcoholic hepatitis: a new primate model. Science. 1973 Nov 16;182(4113):712–713. doi: 10.1126/science.182.4113.712. [DOI] [PubMed] [Google Scholar]
  18. Rubin E., Lieber C. S. Fatty liver, alcoholic hepatitis and cirrhosis produced by alcohol in primates. N Engl J Med. 1974 Jan 17;290(3):128–135. doi: 10.1056/NEJM197401172900303. [DOI] [PubMed] [Google Scholar]
  19. Schnaitman C., Greenawalt J. W. Enzymatic properties of the inner and outer membranes of rat liver mitochondria. J Cell Biol. 1968 Jul;38(1):158–175. doi: 10.1083/jcb.38.1.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Taraschi T. F., Ellingson J. S., Wu A., Zimmerman R., Rubin E. Membrane tolerance to ethanol is rapidly lost after withdrawal: a model for studies of membrane adaptation. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3669–3673. doi: 10.1073/pnas.83.11.3669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Taraschi T. F., Ellingson J. S., Wu A., Zimmerman R., Rubin E. Phosphatidylinositol from ethanol-fed rats confers membrane tolerance to ethanol. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9398–9402. doi: 10.1073/pnas.83.24.9398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Taraschi T. F., Rubin E. Effects of ethanol on the chemical and structural properties of biologic membranes. Lab Invest. 1985 Feb;52(2):120–131. [PubMed] [Google Scholar]
  23. Taraschi T. F., Wu A., Rubin E. Phospholipid spin probes measure the effects of ethanol on the molecular order of liver microsomes. Biochemistry. 1985 Dec 3;24(25):7096–7101. doi: 10.1021/bi00346a012. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Waring A. J., Rottenberg H., Ohnishi T., Rubin E. Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2582–2586. doi: 10.1073/pnas.78.4.2582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Waring A. J., Rottenberg H., Ohnishi T., Rubin E. The effect of chronic ethanol consumption on temperature-dependent physical properties of liver mitochondrial membranes. Arch Biochem Biophys. 1982 Jun;216(1):51–61. doi: 10.1016/0003-9861(82)90187-4. [DOI] [PubMed] [Google Scholar]

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