Pyruvate-dependent oxidative phosphorylation in erythroid and myeloid tumor mitochondria

The pyruvate-supported oxidative phosphorylation activity was determined in mitochondria isolated from the fast-growing erythroid and myeloid tumors of hematopoietic origin. Normal bone marrow and liver mitochondria were used for comparison. In the absence of primers, both tumor mitochondria exhibited a pyruvate-dependent respiratory state 4/state 3 transition, which was totally inhibited by either alpha-cyanocinnamate or arsenite. The transition rate increased in a concentration-dependent manner from 5 to 100 microM pyruvate, where the maximum activity was reached. Increasing the concentration to 500 microM and beyond, however, resulted in decreasing state 3 respiratory jump with little or no jump demonstrable at concentrations above 5 mM. Moreover, the addition of high concentrations of pyruvate during the respiratory state 3 caused a blockage of that state which was reestablished by the addition of succinate or alpha-ketoglutarate. These results clearly show the capacity of erythroid and myeloid tumor mitochondria to actively utilize low concentrations of pyruvate to support their oxidative phosphorylation activity. The reason for the absence of activity found with the high concentration, however, is not readily apparent.