title: Chronic ethanol feeding causes depression of mitochondrial elongation factor Tu in the rat liver: implications for the mitochondrial ribosome.
abstract: Chronic ethanol feeding is known to negatively impact hepatic energy metabolism. Previous studies have indicated that the underlying lesion responsible for this may lie at the level of the mitoribosome. The aim of this study was to characterize the structure of the hepatic mitoribosome in alcoholic male rats and their isocalorically paired controls. Our experiments revealed that chronic ethanol feeding resulted in a significant depletion of both structural (death-associated protein 3) and functional [elongation factor thermo unstable (EF-Tu)] mitoribosomal proteins. In addition, significant increases were found in nucleotide elongation factor thermo stable (EF-Ts) and structural mitochondrial ribosomal protein L12 (MRPL12). The increase in MRPL12 was found to correlate with an increase in the levels of the 39S large mitoribosomal subunit. These changes were accompanied by decreased levels of nuclear- and mitochondrially encoded respiratory subunits, decreased amounts of intact respiratory complexes, decreased hepatic ATP levels, and depressed mitochondrial translation. Mathematical modeling of ethanol-mediated changes in EF-Tu and EF-Ts using prederived kinetic data predicted that the ethanol-mediated decrease in EF-Tu levels could completely account for the impaired mitochondrial protein synthesis. In conclusion, chronic ethanol feeding results in a depletion of mitochondrial EF-Tu levels within the liver that is mathematically predicted to be responsible for the impaired mitochondrial protein synthesis seen in alcoholic animals.
authors.affiliation: Dept. of Pathology, Anatomy and Cell Biology, Thomas Jefferson Univ., Philadelphia, PA 19107, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Weiser
authors.forename: Gregory
authors.initials: G
authors.lastname: Gonye
authors.forename: Peter
authors.initials: P
authors.lastname: Sykora
authors.forename: Sara
authors.initials: S
authors.lastname: Crumm
authors.forename: Alan
authors.initials: A
authors.lastname: Cahill
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D000431:Ethanol / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D015233:Models, Statistical; D009245:NADH Dehydrogenase / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D010444:Peptide Elongation Factor Tu / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000227:Adenine Nucleotides; D002492:Central Nervous System Depressants; D000431:Ethanol; D009245:NADH Dehydrogenase; D010444:Peptide Elongation Factor Tu