OXYGEN DEPENDENCE OF MITOCHONDRIAL-FUNCTION MEASURED BY HIGH-RESOLUTION RESPIROMETRY IN LONG-TERM HYPOXIC RATS

Respiration and oxidative phosphorylation were investigated in Lightly coupled mitochondria isolated from liver and heart of rats submitted to a simulated altitude of 4,400 m for 14-15 mo and their correspondin g controls at sea level. High-resolution respirometry was utilized to determine the apparent Michaelis-Menten constant for ADP and O-2 (K-m- ADP and K-m-O-2, respectively), the latter under active and resting st ates of mitochondrial respiration. The K-m-O-2 in mitochondria isolate d fi am 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 mu M in heart and liver mitochondria, respectively. The K-m-O -2 values found in the active state suggest a role for the normally oc curring intracellular Pot range reported in the literature in the regu lation of cellular respiration. No changes were found in the ADP or O- 2 dependence of respiration in the mitochondria isolated from long-ter m 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.