Mitochondrial Free Fatty Acid Research Articles

The composition of free fatty acids and mitochondrial activity in seedlings of winter cereals under cold shock

Cold shock (-4° C, 1 h) induces qualitative and quantitative changes in the composition of free fatty acids in mitochondria of winter-hardy cereals (Secale cereale L.,Triticum aestivum L.). The amount of these compounds and the degree of their unsaturation increases. Simultaneously, a marked change occurs in the oxidative and phophorylative activities of the mitochondria: respiratory control decreases, respiration in state 4 and antimycin A-resistant respiration increase. The changes in mitochondrial activity are presumed to be caused by endogenous free fatty acids, the amount of which is increased because of phospholipase activity.

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 elevated, 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, C18:0 and 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.

Lipid metabolism in myocardial ischaemia: Correlation between tissue and mitochondrial free fatty acid (FFA)_contents and mitochondrial oxidative phosphorylation

Lipid metabolism in myocardial ischaemia: Correlation between tissue and mitochondrial free fatty acid (FFA)_contents and mitochondrial oxidative phosphorylation

Dual action of succinate in the reduction of acetoacetate by rat liver mitochondria

1. 1. Acetoacetate reduction by rat liver mitochondria in the presence of different succinate concentrations has been studied. 2. 2. At low succinate concentrations (0.5-1 mM) the oxidation of mitochondrial free fatty acids, sparked by succinate, plays a prominent role in the acetoacetate reduction. 3. 3. At higher succinate concentrations the reducing equivalents for acetoacetate reduction derive from succinate via the ‘ reversal’ pathway. 4. 4. Furthermore in the presence of high succinate concentrations (lomM) fatty acid oxidation is almost completely inhibited.

The role of fatty acids in mitochondrial changes during liver ischemia

Exposure of rat liver to periods of ischemia results in a progressive increase in mitochondrial free fatty acids (FFA). The levels increase some 6–7-fold when the liver has been ischemic either for 2 hr at 38 ° or 13 hr at 24 °. A decline in respiratory control (rate of O 2 uptake with ADP/rate of O 2 uptake without ADP) parallels the rise in FFA at both temperatures. Significant depression of respiratory control is observed when comparable amounts of FFA are added to normal mitochondria. Bovine serum albumin (BSA), which restores respiratory control to a considerable degree and enhances the stability of mitochondria isolated from ischemic tissue, reduces the FFA levels about 70%. Despite the presence of BSA during isolation and testing of the mitochondria, there is still a gradual decline in the respiratory control ratio over a period of ischemia lasting several hours, primarily because of a diminution in the state 3 rate of respiration. The levels of mitochondrial phosphatidyl ethanolamine decreased somewhat, but the percentage change was small. Phosphatidyl choline remained essentially unchanged. A more significant decrease in cardiolipin was observed. Part of this change must be ascribed to dilution of the mitochondria by increased microsomal contamination. The data suggest that mitochondrial changes during ischemia involve (a) a BSA-reversible phase produced by FFA released by lipolysis, and (b) a further change, not reversed by BSA, which may be due to loss of essential mitochondrial lipid like cardiolipin, the presence of lysophosphatides, or proteolysis. Morphological changes in mitochondria in liver sections are consistent with these interpretations.

Effects of guanidine derivatives on mitochondrial function

Long chain free fatty acids interfere with the inhibitory action of phenethylbiguanide and related compounds on mitochondrial respiration in vitro. This interference depends on binding of fatty acids to mitochondria and diminishes with decreasing chain length. Reversal of guanidine-derivative inhibition by fatty acids differs from that caused by dinitrophenol in that the effect of fatty acid is achieved without alteration in coupling or respiratory control. The binding of phenethylbiguanide to mitochondria is inhibited by both fatty acid and dinitrophenol. Serum albumin potentiates the inhibitory potency of guanidine derivatives, probably by removing endogenous mitochondrial free fatty acids.