Mitochondrion Cardiolipin

The mitochondrion has an outer and an inner membrane (Figure 1). The outer membrane contains pores formed from a protein, porin, which allow exchange of molecules with molecular weights up to about 2,000 between the cytosol and the intermembrane space. The inner membrane is extensively invaginated to increase its surface area. It has a different lipid composition from the outer membrane and is rich in the acidic phospholipid cardiolipin (diphosphatidyl-glycerol) which is only found in animal cells in mitochondria. Cardiolipin confers good electrical insulating properties on the inner membrane which is impermeable... 

We directed our initial attention to the mitochondrion-specific phospholipid, cardiolipin because it is particularly rich in polyunsaturated fatty acids which are vulnerable to oxidative attack. It seemed reasonable to speculate that mitochondrial cardiolipin may degrade by the enhanced peroxidation reactions during apoptotic cell death,... 

The outer membrane of the mitochondrion contains a large number of pores, so that molecules with molecular weights less than 1,000 can pass from the cytoplasm into the intermembrane space without any specialized transport mechanisms. This means, for example, that NADH, ADP, and inorganic phosphate can reach the intermembrane space from the cytoplasm while NAD and ATP can reach the cytoplasm. The inner membrane is much less permeable, in part due to the presence of a specialized membrane lipid known as cardiolipin (meaning heart lipid—cardiac cells have a large number of mitochondria). The inner membrane of the mitochondrion is highly folded into cristae, so that it has an interleaved appearance in the electron microscope. 

It should not be assumed that hydroxy fatty acids are biologically inactive. Hydroxy fatty acids are chemotactic and vasoactive. Such fatty acids could perturb phospholipids in membranes. For instance, cardiolipin containing hydroxy-linoleic acid does not support the electron transport coupled to ATP production of the mitochondrion. 5-Hydroxy de-canoic acid is a well-known inhibitor of the K -ATP channel. Isoprostanes, trihydroxy oxidation products of arachi-donic acid, are vasoconstrictors (76). 13-Hydroxy linoleic acid (13-HODE) is a lipoxygenase-derived metabolite that influences the thromboresistant properties of endothelial cells in culture (77). However, there is some doubt about the tme nature of these hydroxy-fatty acids generated by the cells, as there are several GSH- and NADPH-dependent pathways that can immediately reduce hydroperoxy- to hydroxy-fatty acids. Furthermore, the reduction step of the analytical method would have converted the hydroperoxy- to a hydroxy-group. Nevertheless, much work remains to be done to determine the relative contribution of hydroperoxy- and hydroxy- to the biological effects of fried fat, and in particular their role in endothelial dysfunction and activation of factor VII. There have been earlier suggestions that a diet rich in lipid peroxidation products may lead to atherosclerosis and CHD (34,78). 

The method of estimating the amount of inner membrane in mitochondria has varied from investigation to investigation. In a few cases morphometric analysis of the amount of membrane per square micrometer of mitochondrial profile has been made in some, inner membrane is measured in terms of the phospholipid or cardiolipin content of the mitochondrion, the latter being particularly suitable since cardiolipin is fairly well localized in the inner membrane of mitochondria in others, mitochondria have been disrupted by osmotic shock, detergents, and sonication, and the protein content of the insoluble fraction has then been... 

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