Hypoxia-reoxygenation differentially alters the thermal sensitivity of complex I basal and maximal mitochondrial oxidative capacity

Hypoxia-reoxygenation (H-R) transitions and temperature fluctuations occur frequently in biological systems and likely interact to alter cell function. To test how H-R modulates mitochondrial function at different temperatures we measured the effects of H-R on isolated fish liver mitochondrial oxidation rates over a wide temperature range (5–25 °C). Subsequently, the mechanisms underlying H-R induced mitochondrial responses were examined. H-R inhibited the complex I (CI) maximal (state 3) and stimulated the basal (state 4) mitochondrial oxidation rates with temperature enhancing both effects. As a result, the thermal sensitivity (Q10) for CI maximal respiration was reduced while that for basal respiration was increased by H-R. H-R reduced both the coupling and phosphorylation efficiencies more profoundly at high temperature suggesting that mitochondria were more resistant to H-R at low temperature. The H-R induced mitochondrial impairments were associated with increased reactive oxygen species (ROS) production and proton leak, dissipation of membrane potential, and loss of structural integrity of the organelles. Overall, our study provides insight into the mechanisms of H-R induced mitochondrial morphofunctional disruption and shows that the moderation of effects of H-R on oxidative phosphorylation by temperature depends on the functional state.