Effect of oxygen tension on cellular energetics.

Simultaneous measurements of the mitochondrial [NAD+]/[NADH], the cytoplasmic [ATP]/[ADP] x [Pi], and the respiratory rate were carried out in suspensions of cultured kidney cells in a range of defined oxygen tensions. The results show that as the extracellular oxygen concentration falls there is a decrease in the respiratory rate, which is accompanied by a decrease in the [ATP]/[ADP] and a progressive reduction of cytochrome c. Even at low O2 tensions the mitochondrial respiratory chain between the NAD couple and cytochrome c remains at near equilibrium with the ATP synthesizing reactions. It is concluded that limited oxygen supply affects cellular metabolism at much higher concentrations than the P50 value for the oxygen dependence of respiration, but the respiratory rate remains relatively unchanged due to compensatory changes in the [ATP]/[ADP] X [Pi] and progressive reduction of cytochrome c. These metabolic changes may form a basis for the phenomenon of tissue oxygen sensing at near physiological oxygen tensions.