Lipids of dystrophic and normal mouse muscle: whole tissue and particulate fractions

Myofibrillar, mitochondrial, and microsomal fractions were prepared from normal and dystrophic mouse limb muscle by differential centrifugation and analyzed for phospholipids and cholesterol. Fatty acids and aldehydes of neutral lipids and of phospholipids from whole muscle and particulate fractions were also determined. Normal microsomes contained more lecithin and less total ethanolamine phospholipids and cardiolipin than mitochondria. The myofibrils had an intermediate phospholipid composition, but their cholesterol-phospholipid ratio was smaller than that of the other two fractions. Except for an increased percentage of phosphatidalethanolamine in the dystrophic mitochondria, only the composition of the dystrophic microsomes differed from normal by containing less lecithin but more total ethanolamine phospholipid, phosphatidalethanolamine, sphingomyelin, and cholesterol. No significant differences were found in the fatty acid composition of neutral lipid extracts from normal and dystrophic preparations, but there was a significant decrease in the percentage of 22:6 in phospholipids from both dystrophic whole muscle and microsomes (-25% and -37%, respectively), whereas the 20:4 content was unaltered. By contrast, the percentages of 18:0 and total fatty aldehyde increased significantly. Phospholipid extracts from all dystrophic samples showed a significant decrease in 16:0 and an increase in 18:1 as compared with the normal.     

Lipid composition of brown adipose tissue mitochondria and microsomes in hyperthyroid rats

1. The effects of triiodothyronine on the lipid composition of rat brown adipose tissue (BAT) mitochondria and microsomes was investigated by high performance liquid chromatography (HPLC). 2. An increase of about 20% was noted in mitochondrial cholesterol and phospholipids, while a decrease of about 20% for both total cholesterol and phospholipids was observed in microsomes from hyperthyroid rats. 3. The BAT phospholipid composition was altered significantly in mitochondria from T3-treated rats with an increase (41%) of cardiolipin and a decrease (18%) in phosphatidylcholine. 4. In microsomes, a decrease by 25% in phosphatidylinositol was accompanied by a similar additional percentage increase in phosphatidylethanolamine. 5. Important alterations in the fatty acid pattern were found in mitochondrial neutral lipids.     

Aging-dependent modification of lipid composition and lipid structural order parameter of hepatic mitochondria

The effect of aging on the lipid composition of hepatic mitochondria has been determined using a rigorously defined group of Fischer 344 rats with known survivorship data. The age groups studied included mature adults as controls (8.5-month, 100% survivorship); an intermediate aged group (17.5-month, 90% survivorship); and an aged group (29-month, 20% survivorship). Lipid extracts of mitochondria were prepared using chloroform-methanol (2:1, by volume) and total phospholipid-P_i, cholesterol (free and esterfied), and phospholipid composition were determined. In the aged animals, total phospholipid-P_i decreased significantly (P = 0.019) whereas cholesterol increased (P = 0.048) with a progressive aging-dependent increase in the molar ratio of cholesterol/phospholipid. The lower total phospholipid content of hepatic mitochondria from the aged 29-month animals was due primarily to decreases in the major phospholipids with the most notable decrease being in cardiolipin (approximately 39%). Steady-state fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene as the probe was used to estimate the lipid structural order parameter of hepatic mitochondria. There was a highly significant (P = 0.01) aging-dependent increase in the lipid structural order parameter which correlated well with the increased molar ratio of cholesterol/phospholipid in the hepatic mitochondria isolated from the aged animals. The data suggest alterations in mitochondrial membrane lipid-protein interactions in aging and are consistent with the hypothesis of impairment of membrane function in the aging process.     

Effect of aging on the activity of the phosphate carrier and on the lipid composition in rat liver mitochondria

The effect of aging on the activity of the phosphate carrier and on the lipid composition in rat liver mitochondria has been investigated. It was found that the rate of phosphate transport in mitochondria from aged rats (28 months old) is significantly reduced (around 40%) compared to that obtained in mitochondria from young control rats (5 months old). Kinetic analysis of the phosphate transport indicates that only the Vmax of this process is affected, while there is no change in the Km values. The lower activity of the phosphate carrier in mitochondria from aged rats is also documented by swelling experiments. The age-related decrement in the activity of the phosphate carrier was found not to be due neither to a change in the endogenous content of phosphate nor to a change in the transmembrane delta pH value. Inhibitor titrations with mersalyl provide no evidence for a lower content of functional phosphate translocase in mitochondria from aged rats. There is no difference either in the respiratory control ratios or in the ADP/O ratios between mitochondria from young and aged animals. The hepatic mitochondrial lipid composition is altered significantly in aged rats: the total cholesterol increases (31%), the phospholipids decrease (12%), and the cholesterol/phospholipid molar ratio increases (44%). Among the phospholipids cardiolipin shows the greatest alteration (30% decrease with age). Alterations were also found in the pattern of fatty acids. The age-related decrement in the activity of the phosphate carrier appears to be dependent on changes in the lipid domain surrounding the carrier protein molecule in the mitochondrial membrane.     

Fatty acid composition of phospholipids in mitochondria and microsomes during diethylnitrosamine carcinogenesis in rat liver

Changes in lipid composition and function of subcellular organelles have been described in transplanted and primary tumours. We examine here the fatty acid composition of individual phospholipids (PL) in hyperplastic nodules and primary hepatoma induced by diethylnitrosamine (DEN), compared to that of normal liver and of transplantable Yoshida AH-130 hepatoma. Phosphatidylcholine and phosphatidylethanolamine fatty acid composition in mitochondria and microsomes from primary hepatoma were markedly different from normal liver; C18:0/C18:1 ratio was lower and the ratio between monosaturated and polyunsaturated fatty acids was higher. Linoleic acid content of mitochondrial cardiolipin, usually very high in normal rat liver, was notably lower in primary hepatoma. Cholesterol/phospholipid ratio in both microsomes and mitochondria from DEN-induced hepatoma was higher than in normal liver. Hyperplastic nodules showed no changes in cholesterol content whereas modifications in fatty acid composition were already observable. These modifications of membrane structure may be related to the functional changes found in nodular cells. Changes in fatty acid composition of membrane phospholipids, occurring in both primary hepatoma and preneoplastic nodules, might be one of the causes for decreased rate of lipid peroxidation peculiar to these tissues.     

The influence of hypothyroidism on the transport of phosphate and on the lipid composition in rat-liver mitochondria.

The influence of hypothyroidism on the transport of phosphate and on the lipid composition in rat-liver mitochondria was examined. It was found that the rate of phosphate transport is reduced (around 40%) in mitochondria from hypothyroid rats compared to that obtained in mitochondria from normal rats. Treatment of hypothyroid rats with thyroid hormone reverses this effect completely. Kinetic analysis of the phosphate transport indicates that only the Vmax of this process is affected, while there is no change in the Km values. The lower rate of phosphate transport in mitochondria from hypothyroid rats is also demonstrated by swelling experiments. There is no significant difference either in the respiratory control ratios or in the ADP/O ratios between these two types of mitochondria. The hepatic mitochondrial lipid composition is altered significantly in hypothyroid rats. The total cholesterol increases, the phospholipids decrease and the cholesterol/phospholipid molar ratio increases (around 40%). Among the phospholipids, cardiolipin shows the greatest alteration (30% decrease in the hypothyroid rats). The phosphatidylethanolamine/phosphatidylcholine ratio also decreases. Alterations were also found in the pattern of fatty acids. These changes in lipid composition may be responsible, at least in part, for the depression of the phosphate carrier activity in mitochondria from hypothyroid rats.     

Enhanced activity of the tricarboxylate carrier and modification of lipids in hepatic mitochondria from hyperthyroid rats

The effect of hyperthyroidism on the activity of the mitochondrial tricarboxylate carrier has been studied. The activity of this transporting system in liver mitochondria was quantitatively determined by the rate of malate-[14C]citrate exchange using the 1,2,3-benzene-tricarboxylate inhibitor stop technique. It has been found that the rate of citrate uptake is significantly enhanced in liver mitochondria from hyperthyroid rats as compared to that obtained in mitochondria from control rats. Kinetic analysis of the malate-citrate exchange reaction indicates that only the Vmax of this transporting process is enhanced, while there is practically no change in the Km values. Inhibitor titrations with the inhibitor palmitoyl-CoA show that mitochondria from hyperthyroid rats require the same concentrations of inhibitor to produce 100% inhibition of citrate uptake as control mitochondria, suggesting that the amount of functional translocase enzyme present is unaffected. The Arrhenius plot characteristics differ for tricarboxylate carrier activity in mitochondria from hyperthyroid rats as compared with control rats in that the break point of the biphasic plot decreases from 18.1 +/- 1.4 degrees C in controls to 12.9 +/- 1.2 degrees C in hyperthyroid animals. The hepatic mitochondrial lipid composition is altered significantly in hyperthyroid rats; the total cholesterol decreases and the phospholipids increase. The liver mitochondrial phospholipid composition is altered significantly in hyperthyroid rats. In particular negatively charged phospholipid cardiolipin increases by more than 50%. Minor alterations were found in the pattern of fatty acids. The thyroid hormone induced change in the activity of the tricarboxylate carrier can be ascribed either to a general modification of membrane lipid composition which increases the membrane fluidity and in turn the mobility of the carrier or to a more localized change of lipid domain (cardiolipin content) surrounding the carrier molecule in the mitochondrial membrane.     

Mitochondrial dysfunction in rat brain with aging Involvement of complex I, reactive oxygen species and cardiolipin

Reactive oxygen species (ROS) are considered a key factor in brain aging process. Mitochondrial respiration is an important site of ROS production and hence a potential contributor to brain functional changes with aging. In this study we examined the effect of aging on complex I activity, oxygen consumption, ROS production and phospholipid composition in rat brain mitochondria. The activity of complex I was reduced by 30% in brain mitochondria from 24 months aged rats relative to young animals. These changes in complex I activity were associated with parallel changes in state 3 respiration. H(2)O(2) generation was significantly increased in mitochondria isolated from aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, decreased by 31% as function of aging, while there was a significant increase in the level of peroxidized cardiolipin. The age-related decrease in complex I activity in brain mitochondria could be reversed by exogenously added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids. It is proposed that aging causes brain mitochondrial complex I dysfunction which can be attributed to ROS-induced cardiolipin oxidation. These findings may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with brain aging.     

Temperature adaptation of biological membranes. Compensation of the molar activity of cytochrome c oxidase in the mitochondrial energy-transducing membrane during thermal acclimation of the carp (cyprinus carpio L.)

The phospholipid composition, fatty acid pattern and cholesterol content are studied in mitochondria of red lateral muscle of carp acclimated to high and low environmental temperatures.The results of the experiments are: mitochondria from cold-acclimated carp contain higher proportions of ethanolamine phosphatides than mitochondria from warm-acclimated fish, the opposite is true for the choline phosphatides. Thus, at constant pH, the membrane phospholipids are slightly more negatively charged at low acclimation temperature. The total plasmalogen content is reduced in the cold; this reduction is caused by a decrease in the proportion of the choline plasmalogens. The ethanolamine phosphoglycerides contain approx. 20% of the alk-1-enyl acyl type, irrespective of the acclimation temperature. There is no temperature-dependent difference in the low proportion of cholesterol.The fatty acids of total mitochondrial phospholipids are characterized by large amounts of the n-3 and n-6 families. The ratio of unsaturated to saturated fatty acids and the unsaturation index are remarkably higher than those reported for comparable mammalian phospholipids. Cold acclimation of carp does not significantly increase the unsaturation of total phospholipids. A fatty acid analysis of the main isolated phospholipids, however, shows that cold acclimation considerably increases unsaturation of the neutral phosphatidylcholine, whereas it dramatically decreases unsaturation of the negatively charged cardiolipin. It is suggested that the observed fatty acid substitution in phosphatidylcholine indicates a temperature-induced fluidity adaptation within the mitochondrial lipid bilayer, whereas the inverse acclimation pattern of cardiolipin provides a suitable lipid to accommodate the temperature-dependent modifications in the dynamic surface shape of integral membrane proteins.     

Phospholipid composition and fatty acid patterns of isolated phospholipids from rabbit reticulocyte mitochondria

The phospholipid composition and fatty acid patterns of individual phospholipid classes were determined in mitochondria from rabbit reticulocytes. Compared to mitochondria from rat liver reticulocyte, mitochondria exhibit about twice the amount of phospholipids. The phospholipid pattern of reticulocyte mitochondria (phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and cardiolipin) is comparable with other mitochondrial species. Mitochondrial fractions from reticulocytes are characterized, however, by an additional content of sphingomyelin. This sphingomyelin differs in its fatty acid composition from the sphingomyelin of the plasma membrane. The fatty acid patterns of all other phospholipids essentially correspond to those of mitochondria from other sources and to those of plasma membranes as well.     

Effect of Aging on the Metabolism of Pyruvate and 3-Hydroxybutyrate in Nonsynaptic and Synaptic Mitochondria from Rat Brain

Abstract: Age-dependent changes in the oxidative metabolism in nonsynaptic and synaptic mitochondria from brains of 3, 12, and 24-month-old rats were investigated. When pyruvate and malate were used in conjunction as substrates, a significant reduction in State 3 respiration was observed in both mitochondrial populations from 12-and 24-month-old rats compared with 3-month-old animals. A similar age-dependent reduction in the oxidation of [1-¹¹C]pyruvate was also observed in nonsynaptic and synaptic mitochondria from senescent rats. Pyruvate dehydrogenase complex activity (both active and total) was, however, not decreased in the two mitochondrial populations from brains of 3, 12, and 24-month-old rats. When DL-3-hydroxybutyrate plus malate were used as substrates, a decrease in State 3 respiration was observed only in synaptic mitochondria from 24-month-old rats compared with 3- month-old animals. Similarly, an age-dependent reduction in the oxidation of 3-hydroxy[3-¹¹C]butyrate was also observed only in synaptic mitochondria from 12-and 24-month-old rats. However, a significant reduction in the activities of ketone body-metabolizing enzymes, namely, 3-hydroxybutyrate dehydrogenase, 3-ketoacid CoA transferase, and acetoacetyl-CoA thiolase was observed in both mitochondrlal populations from 12- and 24-month-old rats compared with 3 month-old animals. These findings show that specific alterations in oxidative metabolism occur in nonsynaptic and synaptic mitochondria from aging rats. The data also suggest that in addition to alterations in enzyme activities, permeability of anions (e.g. pyruvate) across the inner mitochondrial membrane may be altered in nonsynaptic and synaptic mitochondria from senescent animals.     

Influence of growth hormone and thyroxine on thermotropic effects of respiration and 1-anilino-8-naphthalene sulfonate fluorescence and on lipid composition of cardiac membranes

The effects of hypophysectomy and subsequent administration of growth hormone and/or L-thyroxine on thermotropic properties of State 3 respiration (ADP-induced), cholesterol, phospholipid and fatty acid composition of phospholipid fraction were examined in myocardial mitochondria of rats. Temperature-dependence of 1-anilino-8-naphthalene sulfonate fluorescence was determined in vesicles prepared from lipids of heart mitochondria. Transition temperature obtained from the Arrhenius plots of respiration occurred at 21 and 24°C for heart mitochondria of normal and hypophysectomized rats, respectively. Most notably, after hypophysectomy the rate of respiration was lower below 24°C, but was progressively higher above that temperature when compared to normal rats. The energy of activation was 148 and 36% larger below and above the transition temperature, respectively. Growth hormone restored almost completely the energy of activation and respiratory rates to normal levels. Administration of L-thyroxine, with or without growth hormone, did not significantly change the rate of respiration but decreased the transition temperature to 17.7–17.0°C. Lipid and phospholipid content, as well as percent distribution of phospholipids and their fatty acid composition were not statistically different among the different groups of rats. Only cholesterol content was increased after hypophysectomy. Administration of growth hormone and thyroxine did not significantly change the total unsaturation index of fatty acids, but growth hormone increased the content of arachidonic acid (20 : 4) by 70% but decreased the docosahexaenoic acid (22 : 6) three times which may have a beneficial effect on mitochondrial membranes. These and other results suggest that hormones exert different effects on subcellular organelles in different tissues, like heart and liver.     

Temperature adaptation of biological membranes. The effects of acclimation temperature on the unsaturation of the main neutral and charged phospholipids in mitochondrial membranes of the carp (cyprinus carpio L.)

The phospholipid composition, fatty acid pattern and cholesterol content are studied in mitochondria of red lateral muscle of carp acclimated to high and low environmental temperatures.The results of the experiments are: mitochondria from cold-acclimated carp contain higher proportions of ethanolamine phosphatides than mitochondria from warm-acclimated fish, the opposite is true for the choline phosphatides. Thus, at constant pH, the membrane phospholipids are slightly more negatively charged at low acclimation temperature. The total plasmalogen content is reduced in the cold; this reduction is caused by a decrease in the proportion of the choline plasmalogens. The ethanolamine phosphoglycerides contain approx. 20% of the alk-1-enyl acyl type, irrespective of the acclimation temperature. There is no temperature-dependent difference in the low proportion of cholesterol.The fatty acids of total mitochondrial phospholipids are characterized by large amounts of the $\text{n-3}\text{and}\text{n-6}$ families. The ratio of unsaturated to saturated fatty acids and the unsaturation index are remarkably higher than those reported for comparable mammalian phospholipids. Cold acclimation of carp does not significantly increase the unsaturation of total phospholipids. A fatty acid analysis of the main isolated phospholipids, however, shows that cold acclimation considerably increases unsaturation of the neutral phosphatidylcholine, whereas it dramatically decreases unsaturation of the negatively charged cardiolipin. It is suggested that the observed fatty acid substitution in phosphatidylcholine indicates a temperature-induced fluidity adaptation within the mitochondrial lipid bilayer, whereas the inverse acclimation pattern of cardiolipin provides a suitable lipid to accommodate the temperature-dependent modifications in the dynamic surface shape of integral membrane proteins.     

Composition of the inner mitochondrial membrane of porcine corpus luteum

An inner mitochondrial membrane fraction was prepared from porcine corpus luteum. The concentrations of the respiratory cytochromes, cytochrome P-450scc, cholesterol, ubiquinone, cardiolipin and the total phospholipids were measured. The fatty acid compositions of cardiolipin and the total phospholipid fraction were determined. Comparative data from porcine heart and liver were obtained using the same methods. Differences in both the concentration and the fatty acid composition of the phospholipids were observed between the tissues. It appeared that the phospholipid bilayer was expanded relative to haem a in luteal mitochondria. It is proposed that in the ovary this expansion may be necessary to accommodate cytochrome P-450scc and its substrate, cholesterol.     

Decreased activity of the phosphate carrier and modification of lipids in cardiac mitochondria from senescent rats.

1. A comparative study of the effects of aging on the transport of phosphate and on the lipid composition in cardiac mitochondria isolated from young and aged rats was carried out. 2. Mitochondria from aged rats (26 month old) translocate phosphate much more slowly than do mitochondria from young control rats (4 month old). 3. Kinetic analysis of the phosphate transport show that only the Vmax of this process is decreased while there is no change in the Km value. 4. There is no appreciable difference in either the respiratory control ratios or in the ADP/O ratios between mitochondria from young and aged rats. 5. The heart mitochondrial lipid composition is altered in aged rats; in particular, the cholesterol/phospholipid molar ratio increases and the content of cardiolipin decreases with aging.     

Temperature response of oxygen uptake in brain mitochondria from normal and ischemic rats

Mitochondria isolated from rat brains following 30 min of complete (decapitation) ischemia showed a 3-fold increase in free fatty acid content, but no significant decreases in the total fatty acid or phospholipid content.This free fatty acid increase was associated with an altered mitochondrial function: a 50% inhibition of state 3 (+ ADP) respiration and a decrease in the respiratory control ratio from 5.5 to 3 to 24°C. The P:O ratio remained unchanged at 3, and there was no increase in stage 4 respiration. When glutamate and malate supported respiration was determined as a function of temperature in control mitochondria, the resulting Arrhenius plot of the state 3 respiration was biphasic with a transition temperature around 30°C, while ischemic mitochondria exhibited a linear Arrhenius plot with energy of activation (approximately 10 kcal/mol) similar to that of control mitochondria below the transition temperature.The difference in temperature response between control and ischemic mitochondria reflects a change in mitochondrial lipid composition, and is therefore a functional manifestation of the altered cerebral lipid composition commonly observed during ischemia.     

Age-related changes in mitochondrial membrane composition of rainbow trout (Oncorhynchus mykiss) heart and brain

Membrane composition, particularly of mitochondria, could be a critical factor by determining the propagation of reactions involved in mitochondrial function during periods of high oxidative stress such as rapid growth and aging. Considering that phospholipids not only contribute to the structural and physical properties of biological membranes, but also participate actively in cell signaling and apoptosis, changes affecting either class or fatty acid compositions could affect phospholipid properties and, thus, alter mitochondrial function and cell viability. In the present study, heart and brain mitochondrial membrane phospholipid compositions were analyzed in rainbow trout during the four first years of life, a period characterized by rapid growth and a sustained high metabolic rate. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and phospholipid class compositions of heart and brain mitochondria, and fatty acid compositions of individual phospholipid classes were determined. Rainbow trout heart and brain mitochondria showed different phospholipid compositions (class and fatty acid), likely related to tissue-specific functions. Furthermore, changes in phospholipid class and fatty acid compositions with age were also tissue-dependent. Heart mitochondria had lower proportions of cardiolipin (CL), phosphatidylserine (PS) and phosphatidylinositol, and higher levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) with age. Heart mitochondrial membranes became more unsaturated with age, with a significative increase of peroxidation index in CL, PS and sphingomyelin (SM). Therefore, heart mitochondria became more susceptible to oxidative damage with age. In contrast, brain mitochondrial PC and PS content decreased in 4-year-old animals while there was an increase in the proportion of SM. The three main phospholipid classes in brain (PC, PE and PS) showed decreased n-3 polyunsaturated fatty acids, docosahexaenoic acid and peroxidation index, which indicate a different response of brain mitochondrial lipids to rapid growth and maturation.     

The renal mitochondrial metabolism of 25-hydroxyvitamin D-3: a possible role for phospholipids

The effect of exogenous phospholipids on chick kidney mitochondrial 25-hydroxyvitamin D-3 metabolism was examined. Phosphatidylserine, phosphatidylcholine and phosphatidylinositol had no effect on either the 1- or 24-hydroxylation of 25-hydroxyvitamin D-3. Phosphatidylethanolamine and cardiolipin both brought about a dose-dependent decrease in the 1-hydroxylase activity in mitochondria from vitamin D-deficient chicks but not from vitamin D-replete chicks. There were no major differences in the phospholipid composition of mitochondria from vitamin D-deficient and -replete chicks nor in the fatty acid composition of these phospholipids. Preliminary kinetic studies suggest that cardiolipin acts as a noncompetitive inhibitor of the 1-hydroxylase in mitochondria isolated from vitamin D-deficient chicks. It does not appear to exert its effect by virtue of altering the distribution of substrate or products. Investigation of the effect of fatty acid methyl esters on the hydroxylase activities suggests that it may be the fatty acid moiety of the phospholipid, rather than the phosphate moiety in the polar head group, that is involved in the phospholipid effect on the hydroxylation of 25-hydroxyvitamin D-3.     

Effects of siRNA-dependent knock-down of cardiolipin synthase and tafazzin on mitochondria and proliferation of glioma cells

The mitochondrial phospholipid cardiolipin (CL) has been implicated with mitochondrial morphology, function, and cell proliferation. Changes in CL are often paralleled by changes in the lipid environment of mitochondria that may contribute to mitochondrial function and proliferation. This study aimed to separate the effects of CL content and CL composition from cellular free fatty acid distribution on bioenergetics and proliferation in C6 glioma cells. To this end, cardiolipin synthase and the CL remodelling enzyme, tafazzin, were knocked-down by siRNA in C6 cells. After 72?h of cultivation, we analysed CL composition by means of LC/MS/MS, distribution of cellular fatty acids by means of gas chromatography, and determined oxygen consumption and proliferation. Knock-down of cardiolipin synthase affected the cellular CL content in the presence of linoleic acid (LA) in the culture medium. Knock-down of tafazzin had no consequence with respect to the pattern of cellular fatty acids but caused a decrease in cell proliferation. It significantly changed the distribution of molecular CL species, increased CL content, decreased oxygen consumption, and decreased cell proliferation when cultured in the presence of linoleic acid (LA). The addition of linoleic acid to the culture medium caused significant changes in the pattern of cellular fatty acids and the composition of molecular CL species. These data suggest that tafazzin is required for efficient bioenergetics and for proliferation of glioma cells. Supplementation of fatty acids can be a powerful tool to direct specific changes in these parameters.     

Phosphatidic acid, phosphatidylinositol, phosphatidylserine and cardiolipin in the course of early embryonic development. Fatty acid composition and content in whole toad embryos and in mitochondrial fractions

The fatty acid composition and content of phosphatidylinositol, phosphatidylserine and phosphatidic acid have been studied during the early development of toad embryos. Acidic phospholipids have been analyzed in whole oocytes and embryos and in the following subcellular fractions: yolk platelets, mitochondria and microsomes. Also cardiolipin, a mitochondrial phospholipid, has been analyzed. Gastrula stage embryos have shown, mainly in the mitochondrial fraction, an increase in the content of phosphatidic acid, phosphatidylserine and phosphatidylinositol with respect to unfertilized oocytes. Changes in the distribution of acyl groups of phosphatidic acid have been detected when different subcellular fractions are compared. On the other hand, the phosphatidylserine composition remains unmodified. Arachidonate and stearate are the principal components of phosphatidylinositol. Cardiolipin shows the same composition up to gastrulation and linoleate comprises about 50% of the total acyl groups.