Postnatal development of rat liver mitochondria: State 3 respiration, adenine nucleotide translocase activity, and the net accumulation of adenine nucleotides

Abstract

The postnatal maturation of respiratory activity was studied in mitochondria isolated from livers of newborn rats that had been Caeserean delivered on the 22nd day of gestation. At birth, the State 3 respiratory rate with glutamate + malate (68.1 ± 8.4 ng atoms O/min/ mg protein) was much lower than the 2,4-dinitrophenol-uncoupled rate (112.7 ± 13.3 ng atoms O/min/mg protein). During the first hour of postnatal life, the State 3 rate increased to nearly equal the uncoupled rate, which did not change significantly. The State 4 rate and ADP O ratio did not change. After 1 h postnatal, when State 3 respiration had increased 1.6-fold, the total adenine nucleotide content (ATP + ADP + AMP) had increased 1.8-fold, and adenine nucleotide translocase activity had increased 1.5-fold. However, the total adenine nucleotide content and translocase activity continued to increase between 1 and 4.5 h postnatal in parallel with each other, but long after State 3 respiration had developed maximally. The ability of newborn liver mitochondria to accumulate adenine nucleotides in relation to the maturation of State 3 respiration was studied in vitro. Mitochondria incubated with 1 m m ATP at 30 °C for 10 min doubled their total adenine nucleotide content, and this was correlated with a doubling of the State 3 respiratory rate. The net accumulation of adenine nucleotides was inhibited 76 ± 1.8% by 100 μ m N-ethylmaleimide and to a lesser extent (57 ± 0.5%) by 50 μ m atractyloside. It was concluded that the accumulation of intramitochondrial adenine nucleotides, via the net uptake of ATP or ADP, probably accounted for the postnatal maturation of adenine nucleotide translocase activity and State 3 respiration. The data suggested that the translocase rate varied as a function of a much greater range of intramitochondrial adenine nucleotide contents than did the overall State 3 rate. The low rate of ADP-stimulated respiration at birth may have been limited by the rate of translocase-mediated exchange of newly synthesized ATP for external ADP, and/or by the absolute size of the exchangeable internal adenine nucleotide pool, which may have been submaximal for the F 1-ATPase.