Summary: Acidic phospholipids composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol. They occur primarily in mitochondrial inner membranes and in bacterial plasma membranes. They are the main antigenic components of the Wassermann-type antigen that is used in nontreponemal SYPHILIS SERODIAGNOSIS.

Top Publications

  1. Guenaga J, Wyatt R. Structure-guided alterations of the gp41-directed HIV-1 broadly neutralizing antibody 2F5 reveal new properties regarding its neutralizing function. PLoS Pathog. 2012;8:e1002806 pubmed publisher
    ..The data suggest a new mechanism of action, important for vaccine design, in which the 2F5 CDRH3 contacts and destabilizes the MPER helix downstream of its core epitope to allow induction of the extended-loop conformation. ..
  2. Gold V, Robson A, Bao H, Romantsov T, Duong F, Collinson I. The action of cardiolipin on the bacterial translocon. Proc Natl Acad Sci U S A. 2010;107:10044-9 pubmed publisher
    ..Together, the results provide rare and comprehensive insights into the action of a phospholipid on an essential transport complex, which appears to be relevant to a broad range of energy-dependent reactions occurring at membranes...
  3. Xu Y, Zhang S, Malhotra A, Edelman Novemsky I, Ma J, Kruppa A, et al. Characterization of tafazzin splice variants from humans and fruit flies. J Biol Chem. 2009;284:29230-9 pubmed publisher
  4. Belikova N, Tyurina Y, Borisenko G, Tyurin V, Samhan Arias A, Yanamala N, et al. Heterolytic reduction of fatty acid hydroperoxides by cytochrome c/cardiolipin complexes: antioxidant function in mitochondria. J Am Chem Soc. 2009;131:11288-9 pubmed publisher
    ..Regulation of FFA-OOH metabolism may be an important function of cyt c that is associated with elimination of toxic FFA-OOH and synthesis of physiologically active hydroxy-fatty acids in mitochondria. ..
  5. Bergstrom C, Beales P, Lv Y, Vanderlick T, Groves J. Cytochrome c causes pore formation in cardiolipin-containing membranes. Proc Natl Acad Sci U S A. 2013;110:6269-74 pubmed publisher
    ..Our results suggest that the CL-cyt c interaction may be sufficient to allow cyt c permeation of mitochondrial membranes and that cyt c may contribute to its own escape from mitochondria during apoptosis. ..
  6. Kiebish M, Yang K, Liu X, Mancuso D, Guan S, Zhao Z, et al. Dysfunctional cardiac mitochondrial bioenergetic, lipidomic, and signaling in a murine model of Barth syndrome. J Lipid Res. 2013;54:1312-25 pubmed publisher
    ..Collectively, we identified specific lipidomic, bioenergetic, and signaling alterations in a murine model that parallel those of Barth syndrome thereby providing novel insights into the pathophysiology of this debilitating disease. ..
  7. Schlattner U, Tokarska Schlattner M, Ramirez S, Tyurina Y, Amoscato A, Mohammadyani D, et al. Dual function of mitochondrial Nm23-H4 protein in phosphotransfer and intermembrane lipid transfer: a cardiolipin-dependent switch. J Biol Chem. 2013;288:111-21 pubmed publisher
  8. Xiao J, Engel J, Zhang J, Chen M, Manning G, Dixon J. Structural and functional analysis of PTPMT1, a phosphatase required for cardiolipin synthesis. Proc Natl Acad Sci U S A. 2011;108:11860-5 pubmed publisher
  9. Tyurina Y, Tyurin V, Kapralova V, Wasserloos K, Mosher M, Epperly M, et al. Oxidative lipidomics of ?-radiation-induced lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation. Radiat Res. 2011;175:610-21 pubmed publisher

More Information


  1. Claypool S, Koehler C. The complexity of cardiolipin in health and disease. Trends Biochem Sci. 2012;37:32-41 pubmed publisher
    ..In this review, we initially focus on the newly identified players in cardiolipin metabolism and then shift our attention to how changes in cardiolipin metabolism contribute to human disease. ..
  2. Schlame M, Ren M. The role of cardiolipin in the structural organization of mitochondrial membranes. Biochim Biophys Acta. 2009;1788:2080-3 pubmed publisher
    ..e. the formation of uniformly substituted molecular species, may reduce the energy barrier of the assembly process. ..
  3. Gonzalvez F, D Aurelio M, Boutant M, Moustapha A, Puech J, Landes T, et al. Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. Biochim Biophys Acta. 2013;1832:1194-206 pubmed publisher
    ..In Barth syndrome, an X chromosome-linked cardiomyopathy caused by tafazzin mutations, cardiolipins display acyl chain modifications and are present at abnormally low concentrations, whereas monolysocardiolipin ..
  4. Petrosillo G, Moro N, Paradies V, Ruggiero F, Paradies G. Increased susceptibility to Ca(2+)-induced permeability transition and to cytochrome c release in rat heart mitochondria with aging: effect of melatonin. J Pineal Res. 2010;48:340-6 pubmed publisher
    ..Our results might have implications in the necrotic and apoptotic myocytes cell death in aged myocardium, particularly in ischemia/reperfusion injury...
  5. Korytowski W, Basova L, Pilat A, Kernstock R, Girotti A. Permeabilization of the mitochondrial outer membrane by Bax/truncated Bid (tBid) proteins as sensitized by cardiolipin hydroperoxide translocation: mechanistic implications for the intrinsic pathway of oxidative apoptosis. J Biol Chem. 2011;286:26334-43 pubmed publisher
    ..These findings provide new mechanistic insights into the role of CL oxidation in the intrinsic pathway of oxidative apoptosis. ..
  6. Zachman D, Chicco A, McCune S, Murphy R, Moore R, Sparagna G. The role of calcium-independent phospholipase A2 in cardiolipin remodeling in the spontaneously hypertensive heart failure rat heart. J Lipid Res. 2010;51:525-34 pubmed publisher
  7. Paradies G, Petrosillo G, Paradies V, Ruggiero F. Oxidative stress, mitochondrial bioenergetics, and cardiolipin in aging. Free Radic Biol Med. 2010;48:1286-95 pubmed publisher
    ..In this review, we discuss several aspects of mitochondrial bioenergetic alterations in aging and the role played by reactive oxygen species and cardiolipin in these alterations. ..
  8. Osman C, Haag M, Wieland F, Brugger B, Langer T. A mitochondrial phosphatase required for cardiolipin biosynthesis: the PGP phosphatase Gep4. EMBO J. 2010;29:1976-87 pubmed publisher
    ..Our experiments provide the framework for the further dissection of mechanisms that are required for accumulation and maintenance of CL levels in mitochondria. ..
  9. Ban T, Heymann J, Song Z, Hinshaw J, Chan D. OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation. Hum Mol Genet. 2010;19:2113-22 pubmed publisher
    ..These findings indicate that interaction of OPA1 with membranes can stimulate higher order assembly, enhance GTP hydrolysis and lead to membrane deformation into tubules. ..
  10. Taylor W, Hatch G. Identification of the human mitochondrial linoleoyl-coenzyme A monolysocardiolipin acyltransferase (MLCL AT-1). J Biol Chem. 2009;284:30360-71 pubmed publisher
    ..The results identify MLCL AT-1 as a human mitochondrial monolysocardiolipin acyltransferase involved in the remodeling of cardiolipin. ..
  11. Schug Z, Gottlieb E. Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis. Biochim Biophys Acta. 2009;1788:2022-31 pubmed publisher
    ..It is now apparent that CL acts as a crucial signalling platform from which it orchestrates apoptosis by integrating signals from a variety of death inducing proteins. ..
  12. Beales P, Bergstrom C, Geerts N, Groves J, Vanderlick T. Single vesicle observations of the cardiolipin-cytochrome C interaction: induction of membrane morphology changes. Langmuir. 2011;27:6107-15 pubmed publisher
    ..We discuss the possible biological implications of our observations in relation to the structure and function of mitochondria. ..
  13. Whited K, Baile M, Currier P, Claypool S. Seven functional classes of Barth syndrome mutation. Hum Mol Genet. 2013;22:483-92 pubmed publisher
    ..In sum, our in-depth characterization of the yeast BTHS-mutant panel has identified seven functional classes of BTHS mutation. ..
  14. Ray N, Durairaj L, Chen B, McVerry B, Ryan A, Donahoe M, et al. Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia. Nat Med. 2010;16:1120-1127 pubmed publisher
    ..This discovery opens the door for new therapeutic strategies directed at modulating the abundance or molecular interactions of cardiolipin in pneumonia. ..
  15. Joshi A, Thompson M, Fei N, Huttemann M, Greenberg M. Cardiolipin and mitochondrial phosphatidylethanolamine have overlapping functions in mitochondrial fusion in Saccharomyces cerevisiae. J Biol Chem. 2012;287:17589-97 pubmed publisher
    ..Taken together, these data demonstrate for the first time in vivo that CL and mitochondrial PE are required to maintain tubular mitochondrial morphology and have overlapping functions in mitochondrial fusion. ..
  16. Kashfi K, Mynatt R, Park E, Cook G. Membrane microenvironment regulation of carnitine palmitoyltranferases I and II. Biochem Soc Trans. 2011;39:833-7 pubmed publisher
  17. Marom M, Safonov R, Amram S, Avneon Y, Nachliel E, Gutman M, et al. Interaction of the Tim44 C-terminal domain with negatively charged phospholipids. Biochemistry. 2009;48:11185-95 pubmed publisher
    ..We suggest that helices A1 and A2, in Tim44, jointly promote the association of the protein with acidic phospholipids. ..
  18. Lu Y, Guan Z, Zhao J, Raetz C. Three phosphatidylglycerol-phosphate phosphatases in the inner membrane of Escherichia coli. J Biol Chem. 2011;286:5506-18 pubmed publisher
    ..As growth slows at 42 °C, PGP accumulates to high levels, and the PG content declines. PgpC orthologs are present in many other bacteria. ..
  19. Romantsov T, Guan Z, Wood J. Cardiolipin and the osmotic stress responses of bacteria. Biochim Biophys Acta. 2009;1788:2092-100 pubmed publisher
    ..Varying CL content is a key element of osmotic adaptation by bacteria but much remains to be learned about its roles in the localization and function of osmoregulatory proteins. ..
  20. Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, et al. Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity. Cell Metab. 2010;12:154-65 pubmed publisher
    ..Collectively, these findings identify a key role of ALCAT1 in regulating CL remodeling, mitochondrial dysfunction, and susceptibility to DIO. ..
  21. Sandoval Calderón M, Geiger O, Guan Z, Barona Gomez F, Sohlenkamp C. A eukaryote-like cardiolipin synthase is present in Streptomyces coelicolor and in most actinobacteria. J Biol Chem. 2009;284:17383-90 pubmed publisher
    ..The broad occurrence of putative orthologues of Sco1389 among the actinobacteria suggests that CL synthesis involving a eukaryotic type Cls is common in actinobacteria...
  22. Kiebish M, Bell R, Yang K, Phan T, Zhao Z, Ames W, et al. Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics. J Lipid Res. 2010;51:2153-70 pubmed publisher
    ..We believe this study provides a foundation to investigate cardiolipin metabolism and bioenergetic homeostasis in normal and disease states. ..
  23. Petit P, Dupaigne P, Pariselli F, Gonzalvez F, Etienne F, Rameau C, et al. Interaction of the alpha-helical H6 peptide from the pro-apoptotic protein tBid with cardiolipin. FEBS J. 2009;276:6338-54 pubmed publisher
    ..The active C-terminal fragment of Bid (tBid) translocates to the mitochondria where it interacts with cardiolipins at contact sites and induces the release of cytochrome c by a mechanism that is not yet fully understood...
  24. Zhang J, Guan Z, Murphy A, Wiley S, Perkins G, Worby C, et al. Mitochondrial phosphatase PTPMT1 is essential for cardiolipin biosynthesis. Cell Metab. 2011;13:690-700 pubmed publisher
    ..Our study identifies PTPMT1 as the mammalian PGP phosphatase and points to its role as a regulator of cardiolipin biosynthesis. ..
  25. Houtkooper R, Rodenburg R, Thiels C, van Lenthe H, Stet F, Poll The B, et al. Cardiolipin and monolysocardiolipin analysis in fibroblasts, lymphocytes, and tissues using high-performance liquid chromatography-mass spectrometry as a diagnostic test for Barth syndrome. Anal Biochem. 2009;387:230-7 pubmed publisher
  26. Arnarez C, Marrink S, Periole X. Identification of cardiolipin binding sites on cytochrome c oxidase at the entrance of proton channels. Sci Rep. 2013;3:1263 pubmed publisher
    ..The ubiquitous nature of CL interactions with the components of the OxPhos suggests that this delivery mechanism might extend to the other respiratory complexes. ..
  27. Koprivnjak T, Zhang D, Ernst C, Peschel A, Nauseef W, Weiss J. Characterization of Staphylococcus aureus cardiolipin synthases 1 and 2 and their contribution to accumulation of cardiolipin in stationary phase and within phagocytes. J Bacteriol. 2011;193:4134-42 pubmed publisher
    ..Differences in the relative contributions of Cls1 and Cls2 to CL accumulation under different triggering conditions suggest differences in the role and regulation of these two enzymes...
  28. Gebert N, Joshi A, Kutik S, Becker T, McKenzie M, Guan X, et al. Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome. Curr Biol. 2009;19:2133-9 pubmed publisher
    ..Our findings reveal a new role for cardiolipin in protein sorting at the mitochondrial outer membrane and bear implications for the pathogenesis of Barth syndrome. ..
  29. Malhotra A, Xu Y, Ren M, Schlame M. Formation of molecular species of mitochondrial cardiolipin. 1. A novel transacylation mechanism to shuttle fatty acids between sn-1 and sn-2 positions of multiple phospholipid species. Biochim Biophys Acta. 2009;1791:314-20 pubmed publisher
  30. Sakamoto T, Inoue T, Otomo Y, Yokomori N, Ohno M, Arai H, et al. Deficiency of cardiolipin synthase causes abnormal mitochondrial function and morphology in germ cells of Caenorhabditis elegans. J Biol Chem. 2012;287:4590-601 pubmed publisher
    ..We propose that the contribution of CL to mitochondrial function and morphology is different among the cell types in C. elegans. ..
  31. Zhou M, Morgner N, Barrera N, Politis A, Isaacson S, Matak Vinkovic D, et al. Mass spectrometry of intact V-type ATPases reveals bound lipids and the effects of nucleotide binding. Science. 2011;334:380-385 pubmed publisher
    ..Consequently, we can link specific lipid and nucleotide binding with distinct regulatory roles...
  32. Montessuit S, Somasekharan S, Terrones O, Lucken Ardjomande S, Herzig S, Schwarzenbacher R, et al. Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization. Cell. 2010;142:889-901 pubmed publisher
    ..In cells, overexpression of Drp1 R247A/E delays Bax oligomerization and cell death. Our findings uncover a function of Drp1 and provide insight into the mechanism of Bax oligomerization...
  33. Betaneli V, Petrov E, Schwille P. The role of lipids in VDAC oligomerization. Biophys J. 2012;102:523-31 pubmed publisher
    ..We suggest that the specific lipid composition of the outer mitochondrial membrane might be of crucial relevance and, thus, a potential cue for regulating the oligomeric state of VDAC. ..
  34. Angelini R, Corral P, Lopalco P, Ventosa A, Corcelli A. Novel ether lipid cardiolipins in archaeal membranes of extreme haloalkaliphiles. Biochim Biophys Acta. 2012;1818:1365-73 pubmed publisher
    ..The role of C(25) isopranoid chains in the adaptation to high pH gradients in the presence of very high salt concentrations is discussed...
  35. Corcelli A. The cardiolipin analogues of Archaea. Biochim Biophys Acta. 2009;1788:2101-6 pubmed publisher
  36. Tyurina Y, Tyurin V, Kaynar A, Kapralova V, Wasserloos K, Li J, et al. Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation. Am J Physiol Lung Cell Mol Physiol. 2010;299:L73-85 pubmed publisher
  37. DeVay R, Dominguez Ramirez L, Lackner L, Hoppins S, Stahlberg H, Nunnari J. Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion. J Cell Biol. 2009;186:793-803 pubmed publisher
  38. Acehan D, Malhotra A, Xu Y, Ren M, Stokes D, Schlame M. Cardiolipin affects the supramolecular organization of ATP synthase in mitochondria. Biophys J. 2011;100:2184-92 pubmed publisher
    ..These data suggest that cardiolipin promotes the ribbonlike assembly of ATP synthase dimers and thus affects lateral organization and morphology of the crista membrane. ..
  39. Renner L, Weibel D. Cardiolipin microdomains localize to negatively curved regions of Escherichia coli membranes. Proc Natl Acad Sci U S A. 2011;108:6264-9 pubmed publisher
    ..These studies demonstrate the curvature dependence of CL in membranes and test whether these structures participate in the localization of MinD to regions of negative curvature in cells. ..
  40. Kuroda T, Tani M, Moriguchi A, Tokunaga S, Higuchi T, Kitada S, et al. FMP30 is required for the maintenance of a normal cardiolipin level and mitochondrial morphology in the absence of mitochondrial phosphatidylethanolamine synthesis. Mol Microbiol. 2011;80:248-65 pubmed publisher
    ..These results indicated that Fmp30p is involved in the maintenance of mitochondrial morphology and required for the accumulation of a normal level of CL in the absence of mitochondrial phosphatidylethanolamine synthesis. ..
  41. Macchioni L, Corazzi T, Davidescu M, Francescangeli E, Roberti R, Corazzi L. Cytochrome c redox state influences the binding and release of cytochrome c in model membranes and in brain mitochondria. Mol Cell Biochem. 2010;341:149-57 pubmed publisher
    ..It could weaken the hydrophobic component of cyt c-CL interactions and might function following complex IV inhibition or in oxygen lack, both conditions producing accumulation of reduced cyt c and free fatty acids. ..
  42. Mishra N, Bayer A. Correlation of cell membrane lipid profiles with daptomycin resistance in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2013;57:1082-5 pubmed publisher
    ..01), and reduced carotenoid content (P < 0.05 for 5/9 strains). There were no significant changes in LPG flipping, cardiolipin content, or fatty acid composition among strain pairs. ..
  43. Kim J, Minkler P, Salomon R, Anderson V, Hoppel C. Cardiolipin: characterization of distinct oxidized molecular species. J Lipid Res. 2011;52:125-35 pubmed publisher
    ..These products were barely detectable from radical oxidation either in a liposome bilayer or in thin film. These observations are only possible due to the chromatographic separation of the different oxidized species. ..
  44. Yoshinaga M, Wormer L, Elvert M, Hinrichs K. Novel cardiolipins from uncultured methane-metabolizing archaea. Archaea. 2012;2012:832097 pubmed publisher
    Novel cardiolipins from Archaea were detected by screening the intact polar lipid (IPL) composition of microbial communities associated with methane seepage in deep-sea sediments from the Pakistan margin by high-performance liquid ..
  45. Schwall C, Greenwood V, Alder N. The stability and activity of respiratory Complex II is cardiolipin-dependent. Biochim Biophys Acta. 2012;1817:1588-96 pubmed publisher
  46. Ascenzi P, Polticelli F, Marino M, Santucci R, Coletta M. Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions. IUBMB Life. 2011;63:160-5 pubmed publisher
    ..e., inhibiting lipid peroxidation and hhcytc traslocation). Here, the CL-driven allosteric modulation of hhcytc properties is reviewed, highlighting proapoptotic and antiapoptotic actions ..
  47. Connerth M, Tatsuta T, Haag M, Klecker T, Westermann B, Langer T. Intramitochondrial transport of phosphatidic acid in yeast by a lipid transfer protein. Science. 2012;338:815-8 pubmed publisher
    ..Thus, intramitochondrial lipid trafficking may involve a regulatory feedback mechanism that limits the accumulation of cardiolipin in mitochondria. ..
  48. van Gestel R, Rijken P, Surinova S, O Flaherty M, Heck A, Killian J, et al. The influence of the acyl chain composition of cardiolipin on the stability of mitochondrial complexes; an unexpected effect of cardiolipin in alpha-ketoglutarate dehydrogenase and prohibitin complexes. J Proteomics. 2010;73:806-14 pubmed publisher
    ..The results indicate that the decreased level of complexes in taz1Delta and acb1Deltataz1Delta mitochondria is due to a decreased content of CL or the presence of MLCL. ..
  49. Osman C, Voelker D, Langer T. Making heads or tails of phospholipids in mitochondria. J Cell Biol. 2011;192:7-16 pubmed publisher
    ..The discovery of proteins that regulate mitochondrial membrane lipid composition and of a multiprotein complex tethering ER to mitochondrial membranes has unveiled novel mechanisms of mitochondrial membrane biogenesis. ..
  50. Tan B, Bogdanov M, Zhao J, Dowhan W, Raetz C, Guan Z. Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates. Proc Natl Acad Sci U S A. 2012;109:16504-9 pubmed publisher
    ..Unlike eukaryotic Cls (that use PG and CDP-diacylglycerol as substrates) or ClsA, the combined YmdB-ClsC used PE as the phosphatidyl donor to PG to form CL, which demonstrates a third and unique mode for CL synthesis. ..
  51. Agar C, van Os G, Morgelin M, Sprenger R, Marquart J, Urbanus R, et al. Beta2-glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood. 2010;116:1336-43 pubmed publisher
    ..The conformational change of beta(2)GPI, and the influence of the autoantibodies may have important consequences for our understanding of the antiphospholipid syndrome. ..
  52. Dumas J, Peyta L, Couet C, Servais S. Implication of liver cardiolipins in mitochondrial energy metabolism disorder in cancer cachexia. Biochimie. 2013;95:27-32 pubmed publisher
    ..This mini-review focuses on cardiolipin especially its biosynthesis and remodeling pathways, its relation with mitochondrial energy metabolism and its possible implication in the cancer cachexia syndrome...
  53. Schlame M. Formation of molecular species of mitochondrial cardiolipin 2. A mathematical model of pattern formation by phospholipid transacylation. Biochim Biophys Acta. 2009;1791:321-5 pubmed publisher
    ..It is concluded that acyl-specific cardiolipin patterns could arise from phospholipid transacylations in the tafazzin domain, even if tafazzin itself does not have substrate specificity. ..