Reduced mitochondrial respiration in mouse cerebral cortex during chronic hypoxia.
Respiratory activity and NADH CoQ reductase (complex I) and cytochrome c oxidase (complex IV) activities were measured in free (non-synaptosomal) mitochondria isolated from cerebral cortex of male Balb/c mice exposed to intermittent hypobaric hypoxia (450 Torr; 4300 m) for 21 days and compared to normoxic (sea level) controls. In the hypoxic we found a 47% reduction of oxygen uptake during state 3 (ADP and substrate present), 12% reduction during state 4 (no ADP present) and 20% reduction in the uncoupled respiration rate with pyruvate plus malate as substrates. Respiratory control ratio (RCR) decreased by 24%. No change in the ADP/O ratio was seen. NADH CoQ reductase activity decreased by 30% and cytochrome c oxidase by 17%, suggesting that under conditions of chronic hypoxia, the reductions of mitochondrial respiratory activities are caused, at least in part, by enzymatic alterations of the electron transport chain (complex I and complex IV). The decreased activity of these enzymes could contribute to alterations in neuronal activity by reducing brain energy metabolism during development under conditions of chronic hypoxia.
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D000860:Hypoxia; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D013997:Time Factors
D009243:NAD; D003576:Electron Transport Complex IV