Oxygen dependence of mitochondrial function measured by high-resolution respirometry in long-term hypoxic rats

Respiration and oxidative phosphorylation were investigated in tightly coupled mitochondria isolated from liver and heart of rats submitted to a simulated altitude of 4,400 m for 14-15 mo and their corresponding controls at sea level. High-resolution respirometry was utilized to determine the apparent Michaelis-Menten constant for ADP and O2 (K(m)-ADP and K(m)-O2, respectively), the latter under active and resting states of mitochondrial respiration. The K(m)-O2 in mitochondria isolated from normoxic rats was higher for active (state 3) than for resting (state 4) respiration; the values decreased from 1.5 and 1.7 to 0.25 and 0.30 microM in heart and liver mitochondria, respectively. The K(m)-O2 values found in the active state suggest a role for the normally occurring intracellular PO2 range reported in the literature in the regulation of cellular respiration. No changes were found in the ADP or O2 dependence of respiration in the mitochondria isolated from long-term acclimatized rats compared with their controls, indicating that the intrinsic properties and the efficiency of mitochondria do not change as a consequence of adaptation to hypoxia.