Control of adenine nucleotide translocation in liver mitochondria from ethanol-fed rats

Male rats developed fatty liver after being fed an ethanol-containing diet for 31 days. Liver mitochondria from these animals (ethanol mitochondria) catalyzed ATP synthesis at a slower rate than did mitochondria from pair-fed control rats (control mitochondria). Furthermore, ATP translocation was decreased in ethanol mitochondria and parameters influencing such were investigated. Several experiments indicated that ADP uptake into ethanol mitochondria is not decreased due to inhibition of the adenine nucleotide translocase by either long chain acyl CoA derivatives or unesterified fatty acids. Analyses of endogenous adenine nucleotides in ethanol mitochondria revealed lower ATP concentrations, but no decrease in total adenine nucleotides. In experiments where endogenous ATP was shifted to higher concentrations by incubation with BSA, the rate of ADP translocation was increased, with a linear correlation being observed between endogenous ATP concentrations and the rate of ADP translocation. The depressed ATP concentration in ethanol mitochondria suggests that the ATP synthetase complex is replenishing endogenous ATP at a slower rate. A decrease in the rate of ATP synthesis in ethanol mitochondria is sufficient to explain the decreased ADP translocation.