Studies on the effect of copper deficiency on rat liver mitochondria. III. Effects on adenine nucleotide translocase.
Liver mitochondria from Cu-deficient rats exhibit impaired State 3 respiration (oxygen consumption in the presence of exogenous ADP) compared with Cu-adequate controls, whereas State 4 respiration (oxygen consumption after depletion of exogenous ADP) and ADP/O are unaffected. In view of previous observations (Davies, N.T., Lawrence, C.B., Mills, C.F. and Nicol, F. (1985) Biochim. Biophys. Acta 809, 351-361) it seemed that a decline in cytochrome c oxidase activity (EC 1.9.3.1) could not fully account for these findings. Cu deficiency resulted in a significant decline (40%, P less than 0.01) in [14C]ADP uptake by liver mitochondria which suggests there is a reduced activity of the adenine nucleotide translocase. The reduced translocase activity was not associated with any marked change in fatty-acid composition of either intact mitochondria or inner mitochondrial membranes. Inhibitor titrations with the irreversible inhibitor carboxyatractyloside showed that 'Cu-deficient' mitochondria required the same concentration of inhibitor to produce 100% inhibition of State 3 respiration as control mitochondria, suggesting that the amount of functional translocase enzyme present is unaffected. When the translocase assay was allowed to proceed until equilibrium was established between external and internal nucleotides, it was apparent that the exchangeable adenine nucleotide pool of Cu-deficient mitochondria was 36% lower than in controls. Analysis of mitochondria for their ATP, ADP and AMP contents showed that, whereas the AMP content was unaffected, ATP and ADP contents were 39 and 40% lower, respectively, which resulted in a significantly reduced pool of total adenine nucleotides (ATP + ADP + AMP) and a reduced 'energy charge' [(ATP + 0.5 ADP)/(ATP + ADP + AMP)]. These results are discussed in relation to current concepts of the regulation and control of mitochondrial respiration.
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D003300:Copper / Q000172:deficiency*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D051381:Rats
D000227:Adenine Nucleotides; D005227:Fatty Acids; D003300:Copper; D000226:Mitochondrial ADP, ATP Translocases; D003576:Electron Transport Complex IV; D009713:Nucleotidyltransferases