Localization of oligomycin-sensitive ADP-ATP exchange activity in rat liver mitochondria

Intact rat liver mitochondria catalyze an ADP-ATP exchange which is partially inhibited by oligomycin and dinitrophenol (Wadkins and Lehninger, 1963; Guillory and Slater, 1965). It has been postulated that the dinitrophenol- and oligomycin-sensitive ADP-ATP exchange reaction is catalyzed by the enzyme(s) participating in ATP formation during oxidative phosphorylation (Wadkins and Lehninger, 1958; 1963). However, the presence of large amounts of adenylate kinase and nucleoside diphosphokinase, which catalyze oligomycin-insensitive ADP-ATP exchanges, has rendered further investigation of the oligomycin-sensitive exchange difficult. In this communication it is shown that when rat liver mitochondria are fractionated with digitonin the oligomycin-sensitive ADP-ATP exchange activity is recovered with the inner membrane-matrix fraction, while all of the nucleoside diphosphokinase and adenylate kinase activity is released with the outer membrane. The exchange activity found in the inner membrane-matrix fraction is localized in the inner membrane and is completely inhibited by oligomycin, dinitrophenol, and atractyloside when assayed in the absence of added Mg⁺⁺. Thus, the oligomycin-sensitive ADP-ATP exchange activity observed in intact mitochondria does not appear to be catalyzed by nucleoside diphosphokinase or adenylate kinase.