Journal of Lipid Research Vol. This test is typically performed when a patient experiences unexplained blood clots, recurrent miscarriages, or autoimmune disease symptoms [ 5 ]. Here we study the impact of lipids in the medium on mitochondrial membrane architecture and function by combining LC-MS/MS lipidomics and functional tests with lipid supplementation experiments in an otherwise serum- and lipid-free cell . Cardiolipin is a unique phospholipid, which is almost exclusively localized in the mitochondrial inner membrane where it is synthesized from phosphatidylglycerol and cytidinediphosphate-diacylglycerol. The importance of CL in cardiovascular health is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), which manifests clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. Cardiolipin-cholesterol interactions in the liquid-crystalline phase: a steady-state and time-resolved fluorescence anisotropy study with cis- and trans-parinaric acids as probes. Science, 01 Feb 1958, 127(3294): 339-340 DOI: 10.1126/science.127.3294.339 . CL composition in spinach leaves (A), tobacco leaves (B), mung bean hypocotyls (C), and green and etiolated barley leaves (D). Biochim Biophys Acta Biomembr. TAFAZZIN deficiency results in abnormal mitochondrial cardiolipin quantity and composition and subsequent mitochondrial dysfunction. Patients have reduced concentration and altered composition of cardiolipin, the specific mitochondrial phospholipid, and they have variable clinical findings, often including heart failure, myopathy, neutropenia, and growth retardation. Gregor Oemera, Marie-Luise Edenhofera,b, Katharina Lackner a,c, Geraldine Lemand, Herbert H. Lindnere, Sandrine Dubracd, Johannes Zschockea, Markus A. Kellera*. . Pathological changes in CL amount or species composition can have deleterious consequences for mitochondrial function and trigger the production of reactive oxygen species. The mitochondrial signature phospholipid cardiolipin (CL), the F 1 F o-ATP-synthase, and the 'mitochondrial contact site and cristae organizing system' (MICOS) complex are involved in this process. Concentration and composition changes of cardiolipin have been implicated in pathological conditions including ischemia, hypothyroidism, aging, heart failure and cardioskeletal myopathy. The molecular assembly of cells depends not only on the balance between anabolism and catabolism but to a large degree on the building blocks available in the environment. Here, we used molecular dynamic simulations to quantify the role of cardiolipin on the formation of pores in simple bacterial-like membrane models composed of phosphatidylglycerol . Stretch, crush, and laceration . Unlike the other phospholipids, CL is synthesized almost exclusively within the mitochondrion to yield a nascent form of this phospholipid with non-uniform acyl chains composition [].The synthesis of CL initiates from phosphatidylglicerol (PG) that is transported from the endoplasmic reticulum (ER) to the IMM. The three most abundant fatty acids are labeled with (1), (2), and (3), respectively. Skeletal muscle is comprised of slow and fast fibers that have high and low mitochondrial content, respectively. Sciatic nerve ligation causes impairment of mitochondria associated with changes in distribution, respiration, and cardiolipin composition in related spinal cord neurons . Cardiolipin (CL) is a unique mitochondrial phospholipid that, in skeletal muscle, is enriched with linoleic acid (18:2n6).Together, CL content and CL 18:2n6 composition are critical determinants of mitochondrial function.Skeletal muscle is comprised of slow and fast fibers that have high and low mitochondrial content, respectively. Preview. Lipid Composition for CAR-201 Concentration (mg/ml) Concentration (mM) Molar Ratio Percentage; Cardiolipin (CL) (extracted from bovine heart) (sodium salt) 14.9: 10: 100: Lipid Composition for CAR-202 Concentration (mg/ml) Concentration (mM) Molar Ratio Percentage; Mutations in tafazzin, a cardiolipin-remodeling enzyme that tends to homogenize cardiolipin chains to linoleic acyls (C18:2) in heart and skeletal muscle, hamper mitochondrial function and are associated . The aim of this study was to analyse the interrelationship between CL composition and the proliferation of prostate cells by exposing PC-3 tumour cells to different fatty acids and by analysing the CL . Dramatic changes of cardiolipin molecular species containing docosahexaenoate . Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. The change in the composition of cardiolipin observed following acute ischemia-reperfusion and subsequently in models of congestive heart failure is consistent with this mechanism. Briefly . Cell viability assays were performed to examine the effects . Modulation of cardiolipin composition is likely one of the levers used by cells to optimize energetic yield in highly ATP-demanding tissues. In the mitochondrial membrane cardiolipin plays an important role in . Subtle variations in the lipid composition of mitochondrial membranes can have a profound impact on mitochondrial function. However, even if levels cannot be brought back to normal just . The role of CL and its metabolism in plants are less well understood. A loss of CL content and remodeling of CL's acyl chains is observed in several pathologies. Cardiolipin (CL) is a key phospholipid of the mitochondria. Cardiolipin oxidation has been shown to be involved in mitochondrial dysfunction in insulin resistance, obesity and NAFLD. CL acyl composition was modeled by a two-step calculation: A matrix of all possible CL fragments was aligned to measured MS 2 spectra by "Broyden-Fletcher-Goldfarb-Shanno" minimization. The phospholipid cardiolipin (CL) is an essential constituent of mitochondrial membranes and plays a role in many mitochondrial processes, including respiration and energy conversion. CL is a kind of diphosphatidylglycerol lipid characterized by a glycerol backbone connected to two phosphatidyl lipids, so each molecule has four acyl chains . . Signaling networks monitor . (Wikipedia) Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also . It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism. In this review, we focus on the potential roles . The test requires a blood sample that is usually taken from a vein in the arm. 18:1 Cardiolipin or tetraoleoyl cardiolipin (115404-77-8) is a monounsaturated phospholipid, used as a radiolabeling assay standard and in liposomes. In this context, free fatty acids are considered as modulators of cell proliferation. Together, CL content and CL 18:2n6 composition are critical determinants . PDF. Previous studies with Podospora anserina demonstrated that manipulation of MICOS leads to altered cristae structure and prolongs lifespan. As such, cardiolipin is subject to a high degree of remodeling by phospholipases, acyltransferases, and transacylases that create a fatty acyl profile that tends to be highly tissue‐specific. Barth syndrome, the only known Mendelian disorder of cardiolipin biosynthesis, is caused by pathogenic variants in the TAFAZZIN gene . The heart is rich in cardiolipin, a phospholipid acylated in four sites, predominately with linoleic acid. Mitochondrial cytochrome c oxidase (CcO) is a multisubunit integral membrane complex consisting of 13 dissimilar subunits, as well as three to four tightly bound molecules of cardiolipin (CL). These results shows that CL is a normal plasma component and suggest that the epitopes of antiphospholipid antibodies could include CL or oxidized CL in lipoproteins or in complexes with plasma proteins (e.g., β 2 -glycoprotein I, prothrombin, protein C, or protein S) or with platelet or endothelial surface proteins. Considering the composition of individual components, three strains contained a considerable amount of cardiolipin (10-13% of total phospholipid). The metabolic defect is now known to be due to mutations in . Strikingly, each cell culture medium compositions had a unique effect on the CL composition (Figure 1C). Embedded into the inner membranes of mitochondria, chloroplasts, and bacteria, F o F 1 -ATP synthase produces . Cardiolipin alterations are considered an important contributing factor in mitochondrial dysfunction in multiple tissues in several physiopathological situations[37-39]. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Therefore, lipid composition and distribution can have a major impact on the regulation of cell . High levels can have a protective function and in general there is a negative association between manifestations of these conditions and antibodies against oxCL. Cardiolipin binds selectively to ATP synthase. The monomeric unit of CcO is able to form a dimer and participate in the formation of supercomplexes in the inner mitochondrial membrane. In this study, we used Fourier transform infrared spectroscopy to evaluate the thermal behavior of multi-component . Briefly . - Jul 05, 2016. Despite this overarching regulation, the molecular species of cardiolipin produced are also influenced by dietary lipid composition. Fatty acyl availability modulates cardiolipin composition and alters mitochondrial function in HeLa cells. the respective cardiolipin composition.17 The available lipid pool in particular is often insufficiently accounted for in standard cell culture experiments, leading to gener-alized CL states that are predominantly shaped by the lipid composition of the growth medium that may mask the genetic characteristics of the cells themselves.16 In A tentative formula is presented. Bacteria such as Staphylococcus aureus modify their membrane's cardiolipin composition to resist such types of perturbations that compromise their membrane stability. The molecular assembly of cells depends not only on their balance between anabolism and catabolism, but to a large degree also on the building blocks available in the environment. For this purpose, hepatic cardiolipin composition was analyzed by means of LC/MS/MS, and mitochondrial oxygen consumption was determined by using a Clark-type electrode in a rat model of vitamin B6 deficiency. Two phosphatidyl groups of cardiolipin, the 3-(3-sn-phosphatidyl) and 1-(3-sn-phosphatidyl) moieties of cardiolipin, were isolated by limited hydrolysis with phospholipase C. . . Europe PMC is an archive of life sciences journal literature. RICE FA. Pathological changes in CL amount or species composition can have deleterious consequences for mitochondrial function and trigger the production of reactive . A cardiolipin antibody test detects cardiolipin antibodies in the blood. Peripheral nerve injury arises most frequently from traumatic insults (87 %), surgery (12 %), as well as from chronic or repetitive compression. Cardiolipin is best classified as a complex phosphatidic acid. Barth syndrome is an X-linked recessive disease caused by mutations in the tafazzin gene. Article. For cultured mammalian . Abstract. In heart mitochondria the fatty acid composition of cardiolipin is commonly viewed as highly regulated due to its high levels of linoleic acid (18:2n - 6) and the dominant presence of a 4×18:2 . Cardiolipin (IUPAC name 1,3-bis(sn-3'-phosphatidyl)-sn-glycerol) is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition.It can also be found in the membranes of most bacteria.The name "cardiolipin" is derived from the fact that it was first found in animal hearts. From our simulations, we identify >700 independent cardiolipin binding sites, allowing us to identify the molecular basis of a prototypical cardiolipin binding site, which we validate against structures of bacterial proteins bound to cardiolipin. One of the most critical membrane properties is fluidity, which has been extensively studied, using mainly single component systems. . Cardiolipin (CL) is a negatively charged lipid found predominantly in the inner mitochondrial membrane of eukaryotic cells 1 and in the plasma membrane of some bacteria 2.The CL molecule is . 2020 Feb 28;1862(6):183239. doi: 10.1016/j.bbamem.2020.183239. Cardiolipin is a component of the Venereal Disease Research Laboratory (VDRL) test for syphilis. Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. For cultivated mammalian cells, this is largely determined by the composition of the growth medium used. Download Citation | Phosphatidylglycerol Supplementation Alters Mitochondrial Morphology and Cardiolipin Composition | The pathogenic variant of the TAZ gene is directly associated with Barth . Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also . Buy now. The inner mitochondrial membrane contains the phospholipid cardiolipin, which has been demonstrated to act as a biomarker for a number of diverse pathologies. The cardiolipin component consisted of either one type of cardiolipin species (TMCL, TOCL, BHCL) or a mixture of cardiolipin species that broadly reflected the CL percent composition of healthy (Con; 39% TLCL, 6% TOCL, 5% TMCL) or dystrophic (Dys; 28% TLCL, 17% TOCL, 5% TMCL) skeletal muscle mitochondria (Zibamanzarmofrad et al., 2013). . In light of the diversity of the acyl compositions of mature CL between different . The aim of . Genetic ablation of either remodeling or biosynthesis of cardiolipin caused a substantial drop in the surface density of OXPHOS proteins in the inner membrane of the mouse heart and Drosophila flight muscle . There are actually three types of cardiolipin . Cardiolipins (CLs) belong to a class of ancient phospholipids found in membranes of both prokaryotes and eukaryotes albeit at different locations: they comprise an abundant component of the bacterial plasma membrane, but are confined almost exclusively to mitochondria in eukaryotes (Daum and Vance, 1997; Hoch, 1992; Schlame, 2008). Composition of cardiolipin. Cardiolipin (CL) is a unique mitochondrial phospholipid, containing up to 85 wt% 18:2n-6 in mammals. Fatty acyl availability modulates cardiolipin composition and alters mitochondrial function in HeLa cells. Remodeling of the acyl chains of cardiolipin (CL) is responsible for final molecular composition of mature CL after de novo CL synthesis in mitochondria. Cardiolipin (CL), an anionic phospholipid of the inner mitochondrial membrane, provides essential functions for stabilizing respiratory complexes and is involved in mitochondrial morphogenesis and programmed cell death in animals. the CL composition was quantified (Figure 1B) as described in (7). For example, the composition of 16:1 FA in total fatty acyl chains of CL was substantially decreased (approximately 20 mol %) after 5 day STZ treatment, was reduced by over 60 mol % after 6 day STZ treatment, and was almost nonexistent after 40 days of diabetes. The composition of the molecular species of acidic phospholipids in Escherichia coli B during the late exponential growth phase at 37 degrees C was determined. The cardiolipin component consisted of either one type of cardiolipin species (TMCL, TOCL, BHCL) or a mixture of cardiolipin species that broadly reflected the CL percent composition of healthy (Con; 39% TLCL, 6% TOCL, 5% TMCL) or dystrophic (Dys; 28% TLCL, 17% TOCL, 5% TMCL) skeletal muscle mitochondria (Zibamanzarmofrad et al., 2013). Cardiolipin (CL) is an anionic membrane phospholipid with bipartite structure containing four acyl groups bound to two glycerol moieties, which are linked via two phosphate groups to a third glycerol. TAFAZZIN encodes for an enzyme involved in the final remodeling step of cardiolipin, a key phospholipid localized to the mitochondrial inner membrane. Figures & SI. ( b) The fatty acid composition from ( a) is used to predict a stochastic CL profile . It has been recognized that diet can play a crucial role in PC genesis and progression. Cardiolipin (CL) is a negatively charged lipid found predominantly in the inner mitochondrial membrane of eukaryotic cells 1 and in the plasma membrane of some bacteria 2.The CL molecule is . . Patients have reduced concentration and altered composition of cardiolipin, the specific mitochondrial phospholipid, and they have variable clinical findings, often including heart failure, myopathy, neutropenia, and growth retardation. Fatty Acyl Availability Modulates Cardiolipin Composition and Alters Mitochondrial Function in HeLa Cells . Barth syndrome is a human disease state (an infantile cardiomyopathy) linked to the X-chromosome that has been associated with marked abnormalities in remodelling and thence in the composition of cardiolipin, i.e., a decrease in tetra-linoleoyl molecular species and an accumulation of monolysocardiolipin. Modeled impact of changed fatty acid states on the mitochondrial cardiolipin composition. Mutations in tafazzin, a cardiolipin-remodeling enzyme that tends to homogenize cardiolipin chains to linoleic acyls (C18:2) in heart and skeletal muscle, hamper mitochondrial function and are associated . /cardiolipin-ratio but also generates a complete cardiolipin spectrum allowing the interrogation of the cardiolipin fatty acid composition, which greatly enhances the diagnostic reliability of the assay. Low levels of antibodies reactive with oxidised Cardiolipin (oxCL) in mammals are related to an increased risk of developing cardiovascular diseases, auto-immune diseases or inflammatory conditions. Remodeling of the acyl chains of cardiolipin (CL) is responsible for final molecular composition of mature CL after de novo CL synthesis in mitochondria. The phospholipid cardiolipin (CL) is an essential constituent of mitochondrial membranes and plays a role in many mitochondrial processes, including respiration and energy conversion. Cardiolipin is a unique phospholipid, which is almost exclusively localized in the mitochondrial inner membrane where it is synthesized from phosphatidylglycerol and cytidinediphosphate-diacylglycerol. Pathological changes in CL amount or species composition can have deleterious consequences for mitochondrial function and trigger the production of These results shows that CL is a normal plasma component and suggest that the epitopes of antiphospholipid antibodies could include CL or oxidized CL in lipoproteins or in complexes with plasma proteins (e.g., β 2 -glycoprotein I, prothrombin, protein C, or protein S) or with platelet or endothelial surface proteins. The phospholipid cardiolipin (CL) is an essential constituent of mitochondrial membranes and plays a role in many mitochondrial processes, including respiration and energy conversion. Cardiolipin Biosynthesis and Remodeling. Together, CL content and CL 18:2n6 composition are critical determinants of mitochondrial function. Abstract Cardiolipin (CL) is a unique phospholipid that is almost exclusively localized at the level of the inner mitochondrial membrane (IMM), where it is biosynthesized. The test requires a blood sample that is usually taken from a vein in the arm. Fatty Acyl Availability Modulates Cardiolipin Composition and Alters Mitochondrial Function in HeLa Cells . 2. Cardiolipin (CL) is a phospholipid at the heart of mitochondrial metabolism, which plays a key role in mitochondrial function and bioenergetics. In yeast, the concentration of proteins involved in oxidative phosphorylation (OXPHOS) correlated with the cardiolipin composition. Info & Metrics. Modulation of cardiolipin composition is likely one of the levers used by cells to optimize energetic yield in highly ATP-demanding tissues. Oxidative damages to cardiolipin (CL) and phosphatidylethanolamine (PEA) are also hallmarks of oxidative stress, but the mechanisms of their damage remain obscure. . Signaling networks monitor . 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