Kidney mitochondrial respiration in protein- and energy-malnourished rats

Several lines of evidence show a close association between plasma membrane Na,K-ATPase and mitochondrial respiration. Extending the observation in human erythrocyte membrane (6), Na,K-ATPase activity has been shown to be elevated in kidney microsomal preparations from protein- and energy-malnourished rats (10). Kidney mitochondrial respiration was studied in these rats under various conditions of assay. Sucrose was used as a modifier of mitochondrial morphology and volume to study its effect on these mitochondria. Mitochondrial state 3 respiration was increased by 35% in protein-deficient rats (P less than 0.02). Vmax(ADP) of state 3 respiration was increased by about 47% in protein- as well as energy-restricted rats. Mitochondria from protein- and energy-deficient rats were more tightly coupled as compared to those from control group. Km apparent for (ADP) and (Pi) were elevated in protein- and energy-malnourished rats. The magnitude of increase was much more in energy-deficient rats. Morphological differences between the mitochondria from two dietary manipulations were reflected in differences in the responses of state 3 respiration, Km(ADP), state 4 respiration, and respiratory control ratios to changing sucrose concentrations. This increase in mitochondrial respiration parallels the increased Na,K-ATPase activity in these rats. Increased Km (ADP and Pi) for mitochondrial respiration are perhaps in response to increased availability of these metabolites in the cytosol. The sucrose effect, in addition, distinguishes the morphological differences in mitochondrial membrane due to protein or energy deficiencies. In conclusion, these results, to a great extent, support an association between the activity of Na,K-ATPase and mitochondrial respiration. The study of mechanism(s) which could contribute to the enhancement of mitochondrial respiration will be of general importance to the understanding of regulation of mitochondrial oxidative phosphorylation, and is of particular interest to us.