Effects of chronic ethanol feeding on rat liver mitochondrial energy metabolism.

Chronic alcohol consumption is known to decrease hepatic mitochondrial respiration rate. It was shown here that the proton leak through the mitochondrial inner membrane was unaffected by chronic ethanol treatment. This indicates that changes in proton leak are not responsible for the alterations in respiration found in mitochondria isolated from ethanol-treated rats. Therefore, the lowered coupled respiration rate is solely due to a decrease in the activity of the electron transport chain. However, this alteration was only evident in coupled respiration (i.e. state 4) and was not apparent in uncoupled respiration. Thus, chronic ethanol treatment decreases the activity of the mitochondrial electron transport chain components which have control over coupled, but not uncoupled, respiration. Mitochondrial energy metabolism is regulated by thyroid hormone status. It was shown that the chronic alcohol treatment did not affect the circulating levels of thyroxine. Furthermore, the activity of mitochondrial alpha-glycerophosphate dehydrogenase, which is strongly affected by thyroid hormones, was unaltered by alcohol treatment. Thus, the effects of ethanol treatment on mitochondria occur independently of changes in circulating thyroid hormone levels.