Response of heart mitochondria to hyperthermia: activation at the febrile temperature versus loss of the inner membrane barrier at higher temperatures

Anotacija

Modular kinetic analysis was applied to compare the response of the oxidative phosphorylation system in rat heart mitochondria to different temperatures in a hyperthermic range (40–45 °C vs. 37 °C) aiming to identify the affected modules of the system. The results indicate that increasing the temperature in a febrile range (37–41 °C) slightly activated the mitochondrial function due to stimulation of the respiratory module, while the kinetics of the proton leak and the phosphorylation module was not affected. A very different pattern of changes was induced at slightly higher temperatures (42–45 °C). A severe impairment of the energy transforming function of mitochondria, caused by a sudden disturbance of the membrane barrier function, was observed at 42 °C. Although the state 3 respiration rate at this temperature remained unchanged, proton leak across the inner mitochondrial membrane was substantially increased, the respiratory module being slightly inhibited, and the membrane potential (Δψ) decreased by 8 mV, leading to a partial uncoupling of oxidative phosphorylation and a diminished ATP synthesis (16% lower phosphorylation flux). The further increase of temperature was extremely harmful to the mitochondrial function: after three minutes of incubation at 45 °C, mitochondria became completely uncoupled and were unable to maintain Δψ and to synthesize ATP. To sum it up, energy production in heart mitochondria was slightly activated at temperatures in the febrile range and was drastically impaired at temperatures higher by only a few degrees. Keywords: heart mitochondria, modular kinetic analysis, membrane permeability, hyperthermia, oxidative phosphorylation