Relation of inorganic orthophosphate and adenine dinucleotide phosphate to the Crabtree effect in mitochondria isolated from Ehrlich ascites tumor cells

Mitochondria have been isolated from Ehrlich-Lettre ascites carcinoma cells which are capable of demonstrating glucose-induced inhibition of succinate oxidation. This inhibition usually amounts to 22% of the steady-state or control rate of respiration and can be released by 2,4-dinitrophenol or any of several mitochondrial swelling agents.The data presented suggest that this glucose-induced respiratory inhibition is due to the accumulation of adenine dinucleotide phosphate (ADP) uncomplemented by inorganic orthophosphate (P_i) at the respiratory chain. This ADP is a product of glucose phosphorylation by ATP during hexokinase activity, and may also account for the mitochondrial contraction known to be concurrent with the Crabtree effect.The transport of P_i to the areas of utilization in the cell is implicated as the limiting factor for both respiration and glycolysis under the conditions of the Crabtree effect.The marked deficiency of mitochondrial ATPase activity may be fundamental to the operation of the Crabtree effect, providing glycolysis with little or no competition for the ATP produced by respiration.