Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption.
Chronic ethanol consumption decreases the synthesis of all 13 polypeptides encoded by the hepatic mitochondrial genome. This alteration in mitochondrial protein synthesis is due to modifications in mitochondrial ribosomes. In the current study, the nature of these alterations was investigated by determining some of the hydrodynamic properties, namely sedimentation coefficient, shape, and mass of mitochondrial ribosomes. The effect of ethanol consumption on the capacity for mitochondrial ribosomes to translate proteins was also determined using an in vitro Poly (U) assay system. Rats were fed the Lieber-DeCarli diet for 31 days with ethanol as 36% of total calories. The sedimentation coefficient, measured by sedimentation velocity analyses, was slightly, but significantly lower in ethanol mitochondrial ribosomes (53.2 +/- 0.5S) when compared with pair-fed controls (54.1 +/- 0.5S) (P = 0.04). Mitochondrial ribosomes from ethanol-fed animals also had a greater tendency to dissociate into subunits. The diffusion coefficient, determined by dynamic light scattering, was lower in mitochondrial ribosomes from ethanol-fed rats than pair-fed controls and this indicated a significantly greater diameter for ethanol ribosomes (42.1 +/- 0.2 nm) than for preparations from pair-fed controls (39.1 +/- 0.5 nm; P = 0.008). These alterations to ethanol mitochondrial ribosomes occurred despite no change in molecular mass, which suggested a significant ethanol-related shape change in the ribosomes. The translation capacity of mitochondrial ribosome preparations from ethanol-fed animals was markedly reduced due to dissociation of the monosome into light and heavy subunits. In summary, these observations demonstrate that chronic ethanol consumption causes significant structural and functional alterations to mitochondrial ribosomes. The loss in ribosome function leads to impaired mitochondrial polypeptide synthesis and is an example of a pathology giving rise to an alteration in the mitochondrial ribosome structure.
Patel
Vinood B
VB
Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1016, USA.
Cunningham
Carol C
CC
D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D004058:Diffusion; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000737:chemistry / Q000187:drug effects*; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D012270:Ribosomes / Q000737:chemistry / Q000187:drug effects*
D000431:Ethanol; D008274:Magnesium