Mitochondrial oxidative phosphorylation in low-flow hypoxia: Role of free fatty acids
The mechanism of mitochondrial damage was investigated in hypoxic hearts, perfused at low pressure without exogenous substrate, as a model of myocardial ischaemia. Mitochondrial and tissue free fatty acid (FFA) contents were determined in control hearts (perfused aerobically at a higher pressure, without exogenous substrate), and in the hypoxic hearts; the functional capacities of mitochondria isolated from the two types of tissue were also compared. Mitochondrial FFA contents were found to be evaluated, relative to the controls, after 20 min of low-flow hypoxic perfusion. However, mitochondrial FFA contents were not different in control and hypoxic hearts after 70 min of perfusion. Low-flow hypoxic perfusion for 70 min caused a significant elevation of tissue C16:0, C18:1 FFA fractions, while total FFA and triglyceride contents were also increased. Accumulation of FFA in whole tissue was accompanied by a depression in mitochondrial function. Thus, after 20 min, both tissue FFA contents and ADP/O and RCI values of mitochondria isolated from control and hypoxic hearts were not different, whereas after 70 min, tissue FFA levels were significantly elevated in hypoxic hearts, with an equally significant depression in the function of isolated mitochondria.