Altered Hepatic Mitochondrial Ribosome Structure Following Chronic Ethanol Consumption

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

“…Moreover, this decrease in ADP-stimulated respiration is linked to decreased electron transport in all segments of the respiratory chain as chronic alcohol consumption decreases the activities of all the respiratory complexes, except complex II [41,42]. Several laboratories have presented strong evidence that inhibition of mitochondrial protein synthesis [43] linked to mtDNA damage [44][45][46] and ribosomal defects [47,48] contribute, in part, to decreased functioning of the oxidative phosphorylation system following chronic alcohol consumption. These alterations translate into profound modifications to the mitochondrial proteome that encompass not only losses in the 13 mitochondrial encoded polypeptides, but also decreases in numerous nuclear encoded proteins that make up the oxidative phosphorylation complexes [46].…”

Proteomic Approaches to Identify and Characterize Alterations to the Mitochondrial Proteome in Alcoholic Liver Disease

“…the global mitochondrial proteome, has only recently been investigated (4,5). Early studies by Cunningham and colleagues demonstrated that chronic alcohol consumption decreases the synthesis of the 13 mitochondrial encoded proteins that are components of complexes I, III, IV, and V (6,7) due to defects in mtDNA (4,8,9) and a decrease in functional mitochondrial ribosomes (10,11). It is important to note however that there are well over 600 proteins that comprise the mitochondrial proteome (12,13), and that close to 100 of these are components of the oxidative phosphorylation system, most of which are encoded by the nuclear genome.…”

Alcoholic Liver Disease and the Mitochondrial Ribosome: Methods of Analysis

“…Although a number of potential molecular mechanisms may explain this decrease, one specific mechanism involves the impaired assembly of mitoribosomes. Investigations conducted by the Cunningham lab have revealed that mitoribosomes isolated from young male rats (200 g) fed ethanol (Lieber-DiCarli diet) (4) for 31 d exhibit decreased sedimentation rates through sucrose density gradients when compared with their paired controls (5,6). Further, sedimentation velocity experiments reveal a significant decrease in the average sedimentation coefficient for the intact ethanol mitoribosome (52.2, ethanol-fed; 53.7, control) (6) as well as for the small ribosomal subunit (27.0, ethanol-fed; 28.3, control) (6).…”

“…Investigations conducted by the Cunningham lab have revealed that mitoribosomes isolated from young male rats (200 g) fed ethanol (Lieber-DiCarli diet) (4) for 31 d exhibit decreased sedimentation rates through sucrose density gradients when compared with their paired controls (5,6). Further, sedimentation velocity experiments reveal a significant decrease in the average sedimentation coefficient for the intact ethanol mitoribosome (52.2, ethanol-fed; 53.7, control) (6) as well as for the small ribosomal subunit (27.0, ethanol-fed; 28.3, control) (6). In addition, mitoribosomes isolated from ethanol-fed animals exhibit significant decreases in their translational diffusion coefficients (1.02 × 10 -7 cm 2 s -1 , ethanolfed; 1.10, control) (6), and larger hydrodynamic diameters (42.1 nm, ethanol-fed; 39.1, control) (6).…”

“…In addition, mitoribosomes isolated from ethanol-fed animals exhibit significant decreases in their translational diffusion coefficients (1.02 × 10 -7 cm 2 s -1 , ethanolfed; 1.10, control) (6), and larger hydrodynamic diameters (42.1 nm, ethanol-fed; 39.1, control) (6). These ethanol-elicited alterations in the physicochemical properties of the hepatic mitoribosome are accompanied by significant amounts of disassociation of the intact 55S monosome (8-14%) into its constituent subunits (5,6). Further, in vitro studies on the translation capacity of mitoribosomes have revealed that while total translation activity is depressed by 29% in the ethanol-fed animals relative to the controls, no difference is detected between the two treatment groups in the activity of the intact monosomes (6), which suggests that the decrease in translation activity observed in ethanol-fed animals is caused by either increased disassociation or decreased association of functional ribosomes rather than impaired activity of intact monosomes.…”