Reduced activity of the electron transport chain in liver mitochondria isolated from rats with secondary biliary cirrhosis.
Mitochondrial metabolism was studied in liver mitochondria isolated from rats with secondary biliary cirrhosis induced by bile duct ligation for 5 wk. State 3 oxidation rates were decreased in mitochondrial preparations from bile duct-ligated rats as compared with sham-operated control rats by 63% and 42% using beta-hydroxybutyrate and succinate as substrates, respectively. In contrast, when the substrate was ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine state 3 oxidation rates were not affected by bile duct ligation. Oxidation rates after uncoupling with dinitrophenol were decreased for both beta-hydroxybutyrate and succinate as substrates in mitochondria from bile duct-ligated rats. The phosphate potential was reduced in mitochondria from bile duct-ligated rats (12.5 +/- 0.5 vs. 13.6 +/- 0.2 kcal in control and bile duct-ligated rats, respectively; p less than 0.05). The inner mitochondrial membrane of liver mitochondria from rats with secondary biliary cirrhosis contained three times more cholesterol as compared with control rats, whereas the phospholipid composition was essentially unchanged. Mitochondrial protein content expressed per liver (calculated on the basis of activities of mitochondrial enzymes determined in liver homogenate and in isolated mitochondria) was increased by 50% in bile duct-ligated rats as compared with control rats. In conclusion, the function of the electron transport chain in liver mitochondria isolated from rats with secondary biliary cirrhosis is impaired. This decrease could be related to altered lipid composition of the inner mitochondrial membrane.
Krähenbühl
S
S
Department of Clinical Pharmacology, University of Berne, Switzerland.
Stucki
J
J
Reichen
J
J
D000818:Animals; D001652:Bile Ducts; D002784:Cholesterol / Q000378:metabolism; D004579:Electron Transport; D004734:Energy Metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008026:Ligation; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D011506:Proteins; D002784:Cholesterol; D010100:Oxygen