The Effects of Histones and Other Polycations on Cellular Energetics

Previous studies in this laboratory have revealed inhibitory effects of various basic compounds on adenosine triphosphat,ase systems associated with active cation transport (l-7).During the course of preliminary investigation of a mitochondrial ATPase preparation (8), it was found t'hat very low concentrations of highly purified histone fractions increased ATPase activity in a manner similar to that produced by 2,4-dinitrophenol.This was somewhat unexpected, since a number of studies have shown that histones and other basic compounds inhibit oxygen consumption in mitochondria and phosphorylation mechanisms in nuclei (9, 10).In addition, the polycations markedly depress several enzymes associated w-ith the electron transport chain (ll-13), which presumably accounts for the observed inhibition of respiration in mitochondria (9, 10).Accordingly, the present communications are directed towards a more detailed study of the effects of a number of basic compounds on oxidative phosphorylation reactions in heart and liver mitochondria.This paper describes the effects on respiration, particularly in the absence of a phosphate acceptor system, and on P:O ratios.Paper II concerns the effects on the socalled partial reactions of oxidative phosphorylation.The results obtained suggest the possibility of an extranuclear function for histones.EXPERIMENTAL PROCEDURE Materials ATP, ADP, NAD, cytochrome c (type III), RNase, hexokinase (type IV), trypsin (twice crystallized, type I), soybean trypsin inhibitor (type I-S), protamine sulfate, poly-n-lysine-HBr (140,000 mol.wt., type I) and 2,4-dinitrophenol were obtained from Sigma Chemical Company.The uncoupling agent car-bony1 cyanide m-chlorophenylhydrazone was generously furnished