Lipids in the Assembly of Membrane Proteins and Organization of Protein Supercomplexes: Implications for Lipid-linked Disorders

  • Mikhail Bogdanov
  • Eugenia Mileykovskaya
  • William Dowhan
Part of the Subcellular Biochemistry book series (SCBI, volume 49)


Lipids play important roles in cellular dysfunction leading to disease. Although a major role for phospholipids is in defining the membrane permeability barrier, phospholipids play a central role in a diverse range of cellular processes and therefore are important factors in cellular dysfunction and disease. This review is focused on the role of phospholipids in normal assembly and organization of the membrane proteins, multimeric protein complexes, and higher order supercomplexes. Since lipids have no catalytic activity, it is difficult to determine their function at the molecular level. Lipid function has generally been defined by affects on protein function or cellular processes. Molecular details derived from genetic, biochemical, and structural approaches are presented for involvement of phosphatidylethanolamine and cardiolipin in protein organization. Experimental evidence is presented that changes in phosphatidylethanolamine levels results in misfolding and topological misorientation of membrane proteins leading to dysfunctional proteins. Examples are presented for diseases in which proper protein folding or topological organization is not attained due to either demonstrated or proposed involvement of a lipid. Similar changes in cardiolipin levels affects the structure and function of individual components of the mitochondrial electron transport chain and their organization into supercomplexes resulting in reduced mitochondrial oxidative phosphorylation efficiency and apoptosis. Diseases in which mitochondrial dysfunction has been linked to reduced cardiolipin levels are described. Therefore, understanding the principles governing lipid-dependent assembly and organization of membrane proteins and protein complexes will be useful in developing novel therapeutic approaches for disorders in which lipids play an important role.


Membrane protein folding Phosphatidylethanolamine Cardiolipin Mitochondria Oxidative phosphorylation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abramson, J., Iwata, S. and Kaback, H.R., Lactose permease as a paradigm for membrane transport proteins (Review), Mol Membr Biol 21 (2004) 227–236.PubMedGoogle Scholar
  2. Acehan, D., Xu, Y., Stokes, D.L. and Schlame, M., Comparison of lymphoblast mitochondria from normal subjects and patients with Barth syndrome using electron microscopic tomography, Lab Invest 87 (2007) 40–48.PubMedGoogle Scholar
  3. Aerts, J.M., Ottenhoff, R., Powlson, A.S., Grefhorst, A., van Eijk, M., Dubbelhuis, P.F., Aten, J., Kuipers, F., Serlie, M.J., Wennekes, T., Sethi, J.K., O'Rahilly, S. and Overkleeft, H.S., Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity, Diabetes 56 (2007) 1341–1349.PubMedGoogle Scholar
  4. Alemany, R., Perona, J.S., Sanchez-Dominguez, J.M., Montero, E., Canizares, J., Bressani, R., Escriba, P.V. and Ruiz-Gutierrez, V., G protein-coupled receptor systems and their lipid environment in health disorders during aging, Biochim Biophys Acta 1768 (2007) 964–975.PubMedGoogle Scholar
  5. Andersson, K., Buschard, K., Fredman, P., Kaas, A., Lidstrom, A.M., Madsbad, S., Mortensen, H. and Jan-Eric, M., Patients with insulin-dependent diabetes but not those with non-insulin-dependent diabetes have anti-sulfatide antibodies as determined with a new ELISA assay, Autoimmunity 35 (2002) 463–468.PubMedGoogle Scholar
  6. Annis, M.G., Soucie, E.L., Dlugosz, P.J., Cruz-Aguado, J.A., Penn, L.Z., Leber, B. and Andrews, D.W., Bax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis, Embo J 24 (2005) 2096–2103.PubMedGoogle Scholar
  7. Aridor, M. and Hannan, L.A., Traffic jam: a compendium of human diseases that affect intracellular transport processes, Traffic 1 (2000) 836–851.PubMedGoogle Scholar
  8. Basova, L.V., Kurnikov, I.V., Wang, L., Ritov, V.B., Belikova, N.A., Vlasova, II, Pacheco, A.A., Winnica, D.E., Peterson, J., Bayir, H., Waldeck, D.H. and Kagan, V.E., Cardiolipin switch in mitochondria: shutting off the reduction of cytochrome c and turning on the peroxidase activity, Biochemistry 46 (2007) 3423–3434.Google Scholar
  9. Beja, O. and Bibi, E., Multidrug resistance protein (Mdr)-alkaline phosphatase hybrids in Escherichia coli suggest a major revision in the topology of the C-terminal half of Mdr, J Biol Chem 270 (1995) 12351–12354.PubMedGoogle Scholar
  10. Bogdanov, M. and Dowhan, W., Phospholipid-assisted protein folding: phosphatidylethanolamine is required at a late step of the conformational maturation of the polytopic membrane protein lactose permease, Embo J 17 (1998) 5255–5264.PubMedGoogle Scholar
  11. Bogdanov, M. and Dowhan, W., Lipid-assisted protein folding, J Biol Chem 274 (1999) 36827–36830.PubMedGoogle Scholar
  12. Bogdanov, M., Heacock, P.N. and Dowhan, W., A polytopic membrane protein displays a reversible topology dependent on membrane lipid composition, Embo J 21 (2002) 2107–2116.PubMedGoogle Scholar
  13. Bogdanov, M., Sun, J., Kaback, H.R. and Dowhan, W., A phospholipid acts as a chaperone in assembly of a membrane transport protein, J Biol Chem 271 (1996) 11615–11618.PubMedGoogle Scholar
  14. Bogdanov, M., Umeda, M. and Dowhan, W., Phospholipid-assisted refolding of an integral membrane protein. Minimum structural features for phosphatidylethanolamine to act as a molecular chaperone, J Biol Chem 274 (1999) 12339–12345.PubMedGoogle Scholar
  15. Bogdanov, M., Xie, J., Heacock, P.N. and Dowhan, W., Operation of a lipid-triggered reversible transmembrane molecular switch within a membrane protein, J Biol Chem (2008) Submitted.Google Scholar
  16. Bogdanov, M., Zhang, W., Xie, J. and Dowhan, W., Transmembrane protein topology mapping by the substituted cysteine accessibility method (SCAM(TM)): application to lipid-specific membrane protein topogenesis, Methods 36 (2005) 148–171.PubMedGoogle Scholar
  17. Bornhovd, C., Vogel, F., Neupert, W. and Reichert, A.S., Mitochondrial membrane potential is dependent on the oligomeric state of F1F0-ATP synthase supracomplexes, J Biol Chem 281 (2006) 13990–13998.PubMedGoogle Scholar
  18. Boumans, H., Grivell, L.A. and Berden, J.A., The respiratory chain in yeast behaves as a single functional unit, J Biol Chem 273 (1998) 4872–4877.PubMedGoogle Scholar
  19. Brandner, K., Mick, D.U., Frazier, A.E., Taylor, R.D., Meisinger, C. and Rehling, P., Taz1, an outer mitochondrial membrane protein, affects stability and assembly of inner membrane protein complexes: implications for Barth Syndrome, Mol Biol Cell 16 (2005) 5202–5214.PubMedGoogle Scholar
  20. Brutkiewicz, R.R., Lin, Y., Cho, S., Hwang, Y.K., Sriram, V. and Roberts, T.J., CD1d-mediated antigen presentation to natural killer T (NKT) cells, Crit Rev Immunol 23 (2003) 403–419.PubMedGoogle Scholar
  21. Buschard, K., Blomqvist, M., Osterbye, T. and Fredman, P., Involvement of sulfatide in beta cells and type 1 and type 2 diabetes, Diabetologia 48 (2005) 1957–1962.PubMedGoogle Scholar
  22. Buschard, K., Hanspers, K., Fredman, P. and Reich, E.P., Treatment with sulfatide or its precursor, galactosylceramide, prevents diabetes in NOD mice, Autoimmunity 34 (2001) 9–17.PubMedGoogle Scholar
  23. Cheng, S.H., Gregory, R.J., Marshall, J., Paul, S., Souza, D.W., White, G.A., O'Riordan, C.R. and Smith, A.E., Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis, Cell 63 (1990) 827–834.PubMedGoogle Scholar
  24. Chicco, A.J. and Sparagna, G.C., Role of cardiolipin alterations in mitochondrial dysfunction and disease, Am J Physiol Cell Physiol 292 (2007) C33–C44.PubMedGoogle Scholar
  25. Choo-Smith, L.P. and Surewicz, W.K., The interaction between Alzheimer amyloid beta(1-40) peptide and ganglioside GM1-containing membranes, FEBS Lett 402 (1997) 95–98.PubMedGoogle Scholar
  26. Claypool, S.M., McCaffery, J.M. and Koehler, C.M., Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins, J Cell Biol 174 (2006) 379–390.PubMedGoogle Scholar
  27. Crabbe, M.J., Cataract as a conformational disease – the Maillard reaction, alpha-crystallin and chemotherapy, Cell Mol Biol 44 (1998) 1047–1050.PubMedGoogle Scholar
  28. De Silva, A.D., Park, J.J., Matsuki, N., Stanic, A.K., Brutkiewicz, R.R., Medof, M.E. and Joyce, S., Lipid protein interactions: the assembly of CD1d1 with cellular phospholipids occurs in the endoplasmic reticulum, J Immunol 168 (2002) 723–733.PubMedGoogle Scholar
  29. Debnath, D., Bhattacharya, S. and Chakrabarti, A., Phospholipid assisted folding of a denatured heme protein: effect of phosphatidylethanolamine, Biochem Biophys Res Commun 301 (2003) 979–984.PubMedGoogle Scholar
  30. Delgado-Partin, V.M. and Dalbey, R.E., The proton motive force, acting on acidic residues, promotes translocation of amino-terminal domains of membrane proteins when the hydrophobicity of the translocation signal is low, J Biol Chem 273 (1998) 9927–9934.PubMedGoogle Scholar
  31. Dlugosz, P.J., Billen, L.P., Annis, M.G., Zhu, W., Zhang, Z., Lin, J., Leber, B. and Andrews, D.W., Bcl-2 changes conformation to inhibit Bax oligomerization, EMBO J 25 (2006) 2287–2296.PubMedGoogle Scholar
  32. Dodson, G. and Steiner, D., The role of assembly in insulin's biosynthesis, Curr Opin Struct Biol 8 (1998) 189–194.PubMedGoogle Scholar
  33. Dowhan, W., Molecular basis for membrane phospholipid diversity: Why are there so many lipids? Annu Rev Biochem 66 (1997) 99–232.Google Scholar
  34. Dowhan, W., Bogdanov, M. and Mileykovskaya, E., Functional roles of lipids in membranes. In: Vance, D.E. and Vance, J.E. (Eds.), Biochemistry of Lipids. Lipoproteins and Membranes, 5th Edition, Amsterdam, Elsevier Press, (2008) pp. in press.Google Scholar
  35. Dowhan, W., Mileykovskaya, E. and Bogdanov, M., Diversity and versatility of lipid-protein interactions revealed by molecular genetic approaches, Biochim Biophys Acta 1666 (2004) 19–39.PubMedGoogle Scholar
  36. Drews, J., What's in a number? Nat Rev Drug Discov 5 (2006) 975.PubMedGoogle Scholar
  37. Dudkina, N.V., Sunderhaus, S., Braun, H.P. and Boekema, E.J., Characterization of dimeric ATP synthase and cristae membrane ultrastructure from Saccharomyces and Polytomella mitochondria, FEBS Lett 580 (2006) 3427–3432.PubMedGoogle Scholar
  38. Dunlop, J., Jones, P.C. and Finbow, M.E., Membrane insertion and assembly of ductin: a polytopic channel with dual orientations, Embo J 14 (1995) 3609–3616.PubMedGoogle Scholar
  39. Eidelman, O., BarNoy, S., Razin, M., Zhang, J., McPhie, P., Lee, G., Huang, Z., Sorscher, E.J. and Pollard, H.B., Role for phospholipid interactions in the trafficking defect of Delta F508-CFTR, Biochemistry 41 (2002) 11161–11170.PubMedGoogle Scholar
  40. Ellis, R.J., Do molecular chaperones have to be proteins? Biochem Biophys Res Commun 238 (1997) 687–692.PubMedGoogle Scholar
  41. Elofsson, A. and von Heijne, G., Membrane protein structure: prediction versus reality, Annu Rev Biochem 76 (2007) 125–140.PubMedGoogle Scholar
  42. Epand, R.F., Tokarska-Schlattner, M., Schlattner, U., Wallimann, T. and Epand, R.M., Cardiolipin clusters and membrane domain formation induced by mitochondrial proteins, J Mol Biol 365 (2007) 968–980.PubMedGoogle Scholar
  43. Fadiel, A., Eichenbaum, K.D., Hamza, A., Tan, O., Lee, H.H. and Naftolin, F., Modern pathology: protein mis-folding and mis-processing in complex disease, Curr Protein Pept Sci 8 (2007) 29–37.PubMedGoogle Scholar
  44. Fredman, P., Mansson, J.E., Rynmark, B.M., Josefsen, K., Ekblond, A., Halldner, L., Osterbye, T., Horn, T. and Buschard, K., The glycosphingolipid sulfatide in the islets of Langerhans in rat pancreas is processed through recycling: possible involvement in insulin trafficking, Glycobiology 10 (2000) 39–50.PubMedGoogle Scholar
  45. Frezza, C., Cipolat, S., Martins de Brito, O., Micaroni, M., Beznoussenko, G.V., Rudka, T., Bartoli, D., Polishuck, R.S., Danial, N.N., De Strooper, B. and Scorrano, L., OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion, Cell 126 (2006) 177–189.PubMedGoogle Scholar
  46. Gafvelin, G. and von Heijne, G., Topological "frustration" in multispanning E. coli inner membrane proteins, Cell 77 (1994) 401–412.PubMedGoogle Scholar
  47. Gelman, M.S. and Kopito, R.R., Cystic fibrosis: premature degradation of mutant proteins as a molecular disease mechanism, Methods Mol Biol 232 (2003) 27–37.PubMedGoogle Scholar
  48. Genova, M.L., Bianchi, C. and Lenaz, G., Supercomplex organization of the mitochondrial respiratory chain and the role of the Coenzyme Q pool: pathophysiological implications, Biofactors 25 (2005) 5–20.PubMedGoogle Scholar
  49. Georges, E., Tsuruo, T. and Ling, V., Topology of P-glycoprotein as determined by epitope mapping of MRK-16 monoclonal antibody, J Biol Chem 268 (1993) 1792–1798.PubMedGoogle Scholar
  50. Giraud, M.F., Paumard, P., Soubannier, V., Vaillier, J., Arselin, G., Salin, B., Schaeffer, J., Brethes, D., di Rago, J.P. and Velours, J., Is there a relationship between the supramolecular organization of the mitochondrial ATP synthase and the formation of cristae?, Biochim Biophys Acta 1555 (2002) 174–180.PubMedGoogle Scholar
  51. Gouffi, K., Gerard, F., Santini, C.L. and Wu, L.F., Dual topology of the Escherichia coli TatA protein, J Biol Chem 279 (2004) 11608–11615.PubMedGoogle Scholar
  52. Guan, L. and Kaback, H.R., Lessons from lactose permease, Annu Rev Biophys Biomol Struct 35 (2006) 67–91.PubMedGoogle Scholar
  53. Gumperz, J.E., The ins and outs of CD1 molecules: bringing lipids under immunological surveillance, Traffic 7 (2006) 2–13.PubMedGoogle Scholar
  54. Haines, T.H. and Dencher, N.A., Cardiolipin: a proton trap for oxidative phosphorylation, FEBS Lett 528 (2002) 35–39.PubMedGoogle Scholar
  55. Han, X., Abendschein, D.R., Kelley, J.G. and Gross, R.W., Diabetes-induced changes in specific lipid molecular species in rat myocardium, Biochem J 352 (2000) 79–89.PubMedGoogle Scholar
  56. Harrison, R.S., Sharpe, P.C., Singh, Y. and Fairlie, D.P., Amyloid peptides and proteins in review, Rev Physiol Biochem Pharmacol 159 (2007) 1–77.PubMedGoogle Scholar
  57. Hauff, K.D. and Hatch, G.M., Cardiolipin metabolism and Barth Syndrome, Prog Lipid Res 45 (2006) 91–101.PubMedGoogle Scholar
  58. Hayden, M.R., Tyagi, S.C., Kerklo, M.M. and Nicolls, M.R., Type 2 diabetes mellitus as a conformational disease, JOP 6 (2005) 287–302.PubMedGoogle Scholar
  59. Hegde, R.S., Mastrianni, J.A., Scott, M.R., DeFea, K.A., Tremblay, P., Torchia, M., DeArmond, S.J., Prusiner, S.B. and Lingappa, V.R., A transmembrane form of the prion protein in neurodegenerative disease, Science 279 (1998) 827–834.PubMedGoogle Scholar
  60. Heinemeyer, J., Braun, H.P., Boekema, E.J. and Kouril, R., A structural model of the cytochrome C reductase/oxidase supercomplex from yeast mitochondria, J Biol Chem 282 (2007) 12240–12248.PubMedGoogle Scholar
  61. Hessa, T., White, S.H. and von Heijne, G., Membrane insertion of a potassium-channel voltage sensor, Science 307 (2005) 1427.PubMedGoogle Scholar
  62. Huggett, J., Vaughan-Thomas, A. and Mason, D., The open reading frame of the Na(+)-dependent glutamate transporter GLAST-1 is expressed in bone and a splice variant of this molecule is expressed in bone and brain, FEBS Lett 485 (2000) 13–18.PubMedGoogle Scholar
  63. Hunte, C., Specific protein-lipid interactions in membrane proteins, Biochem Soc Trans 33 (2005) 938–942.PubMedGoogle Scholar
  64. Hunte, C., Solmaz, S., Palsdottir, H. and Wenz, T., A Structural Perspective on Mechanism and Function of the Cytochrome bc (1) Complex, Results Probl Cell Differ (2007).Google Scholar
  65. Ikeda, M., Kida, Y., Ikushiro, S. and Sakaguchi, M., Manipulation of membrane protein topology on the endoplasmic reticulum by a specific ligand in living cells, J. Biochem. 138 (2005) 631–637.PubMedGoogle Scholar
  66. Jakes, K.S., Kienker, P.K., Slatin, S.L. and Finkelstein, A., Translocation of inserted foreign epitopes by a channel-forming protein, Proc Natl Acad Sci USA 95 (1998) 4321–4326.PubMedGoogle Scholar
  67. Jormakka, M., Tornroth, S., Byrne, B. and Iwata, S., Molecular basis of proton motive force generation: structure of formate dehydrogenase-N, Science 295 (2002) 1863–1868.PubMedGoogle Scholar
  68. Joyce, S., CD1d and natural T cells: how their properties jump-start the immune system, Cell Mol Life Sci 58 (2001) 442–469.PubMedGoogle Scholar
  69. Joyce, S., Woods, A.S., Yewdell, J.W., Bennink, J.R., De Silva, A.D., Boesteanu, A., Balk, S.P., Cotter, R.J. and Brutkiewicz, R.R., Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol, Science 279 (1998) 1541–1544.PubMedGoogle Scholar
  70. Kabayama, K., Sato, T., Kitamura, F., Uemura, S., Kang, B.W., Igarashi, Y. and Inokuchi, J., TNFalpha-induced insulin resistance in adipocytes as a membrane microdomain disorder: involvement of ganglioside GM3, Glycobiology 15 (2005) 21–29.PubMedGoogle Scholar
  71. Kabayama, K., Sato, T., Saito, K., Loberto, N., Prinetti, A., Sonnino, S., Kinjo, M., Igarashi, Y. and Inokuchi, J., Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance, Proc Natl Acad Sci USA 104 (2007) 13678–13683.PubMedGoogle Scholar
  72. Kanki, T., Sakaguchi, M., Kitamura, A., Sato, T., Mihara, K. and Hamasaki, N., The tenth membrane region of band 3 is initially exposed to the luminal side of the endoplasmic reticulum and then integrated into a partially folded band 3 intermediate, Biochemistry 41 (2002) 13973–13981.PubMedGoogle Scholar
  73. Kates, M., Syz, J.Y., Gosser, D. and Haines, T.H., pH-dissociation characteristics of cardiolipin and its 2'-deoxy analogue, Lipids 28 (1993) 877–882.PubMedGoogle Scholar
  74. Kim, P.K., Annis, M.G., Dlugosz, P.J., Leber, B. and Andrews, D.W., During apoptosis bcl-2 changes membrane topology at both the endoplasmic reticulum and mitochondria, Mol Cell 14 (2004) 523–529.PubMedGoogle Scholar
  75. Koch, M., Stronge, V.S., Shepherd, D., Gadola, S.D., Mathew, B., Ritter, G., Fersht, A.R., Besra, G.S., Schmidt, R.R., Jones, E.Y. and Cerundolo, V., The crystal structure of human CD1d with and without alpha-galactosylceramide, Nat Immunol 6 (2005) 819–826.PubMedGoogle Scholar
  76. Lambert, C. and Prange, R., Dual topology of the hepatitis B virus large envelope protein: determinants influencing post-translational pre-S translocation, J Biol Chem 276 (2001) 22265–22272.PubMedGoogle Scholar
  77. Lange, C., Nett, J.H., Trumpower, B.L. and Hunte, C., Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure, Embo J 20 (2001) 6591–6600.PubMedGoogle Scholar
  78. Leber, B., Lin, J. and Andrews, D.W., Embedded together: the life and death consequences of interaction of the Bcl-2 family with membranes, Apoptosis 12 (2007) 897–911.PubMedGoogle Scholar
  79. Levy, D., Membrane proteins which exhibit multiple topological orientations, Essays Biochem 31 (1996) 49–60.PubMedGoogle Scholar
  80. Li, G., Chen, S., Thompson, M.N. and Greenberg, M.L., New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome, Biochim Biophys Acta 1771 (2007) 432–441.PubMedGoogle Scholar
  81. Lima, P.R., Baratti, M.O., Chiattone, M.L., Costa, F.F. and Saad, S.T., Band 3Tambau: a de novo mutation in the AE1 gene associated with hereditary spherocytosis. Implications for anion exchange and insertion into the red blood cell membrane, Eur J Haematol 74 (2005) 396–401.PubMedGoogle Scholar
  82. Lin, J.C. and Liu, H.L., Protein conformational diseases: from mechanisms to drug designs, Curr Drug Discov Technol 3 (2006) 145–153.PubMedGoogle Scholar
  83. Linton, K.J. and Higgins, C.F., P-glycoprotein misfolds in Escherichia coli: evidence against alternating-topology models of the transport cycle, Mol Membr Biol 19 (2002) 51–58.PubMedGoogle Scholar
  84. Loo, T.W. and Clarke, D.M., Membrane topology of a cysteine-less mutant of human P-glycoprotein, J Biol Chem 270 (1995) 843–848.PubMedGoogle Scholar
  85. Lu, Y., Turnbull, I.R., Bragin, A., Carveth, K., Verkman, A.S. and Skach, W.R., Reorientation of aquaporin-1 topology during maturation in the endoplasmic reticulum, Mol Biol Cell 11 (2000) 2973–2985.PubMedGoogle Scholar
  86. Lucken-Ardjomande, S. and Martinou, J.C., Newcomers in the process of mitochondrial permeabilization, J Cell Sci 118 (2005) 473–483.PubMedGoogle Scholar
  87. McGinnes, L.W., Reitter, J.N., Gravel, K. and Morrison, T.G., Evidence for mixed membrane topology of the newcastle disease virus fusion protein, J Virol 77 (2003) 1951–1963.PubMedGoogle Scholar
  88. McKenzie, M., Lazarou, M., Thorburn, D.R. and Ryan, M.T., Mitochondrial respiratory chain supercomplexes are destabilized in Barth Syndrome patients, J Mol Biol 361 (2006) 462–469.PubMedGoogle Scholar
  89. Mendoza, J.L. and Thomas, P.J., Building an understanding of cystic fibrosis on the foundation of ABC transporter structures, J Bioenerg Biomembr (2007).Google Scholar
  90. Milenkovic, V.M., Rivera, A., Horling, F. and Weber, B.H., Insertion and topology of normal and mutant bestrophin-1 in the endoplasmic reticulum membrane, J Biol Chem 282 (2007) 1313–1321.PubMedGoogle Scholar
  91. Mileykovskaya, E., Zhang, M. and Dowhan, W., Cardiolipin in energy transducing membranes, Biochemistry (Mosc) 70 (2005) 154–158.Google Scholar
  92. Molano, A., Park, S.H., Chiu, Y.H., Nosseir, S., Bendelac, A. and Tsuji, M., Cutting edge: the IgG response to the circumsporozoite protein is MHC class II-dependent and CD1d-independent: exploring the role of GPIs in NK T cell activation and antimalarial responses, J Immunol 164 (2000) 5005–5009.PubMedGoogle Scholar
  93. Monaco, S., Zanusso, G., Mazzucco, S. and Rizzuto, N., Cerebral amyloidoses: molecular pathways and therapeutic challenges, Curr Med Chem 13 (2006) 1903–1913.PubMedGoogle Scholar
  94. Morillas, M., Swietnicki, W., Gambetti, P. and Surewicz, W.K., Membrane environment alters the conformational structure of the recombinant human prion protein, J Biol Chem 274 (1999) 36859–36865.PubMedGoogle Scholar
  95. Moss, K., Helm, A., Lu, Y., Bragin, A. and Skach, W.R., Coupled translocation events generate topological heterogeneity at the endoplasmic reticulum membrane, Mol Biol Cell 9 (1998) 2681–2697.PubMedGoogle Scholar
  96. Mulugeta, S. and Beers, M.F., Processing of surfactant protein C requires a type II transmembrane topology directed by juxtamembrane positively charged residues, J Biol Chem 278 (2003) 47979–47986.PubMedGoogle Scholar
  97. Mutter, T., Dolinsky, V.W., Ma, B.J., Taylor, W.A. and Hatch, G.M., Thyroxine regulation of monolysocardiolipin acyltransferase activity in rat heart, Biochem J 346 Pt 2 (2000) 403–406.Google Scholar
  98. Nagamori, S., Vazquez-Ibar, J.L., Weinglass, A.B. and Kaback, H.R., In vitro synthesis of lactose permease to probe the mechanism of membrane insertion and folding, J Biol Chem 278 (2003) 14820–14826.PubMedGoogle Scholar
  99. Nilsson, I. and von Heijne, G., Fine-tuning the topology of a polytopic membrane protein: role of positively and negatively charged amino acids, Cell 62 (1990) 1135–1141.PubMedGoogle Scholar
  100. Osterbye, T., Jorgensen, K.H., Fredman, P., Tranum-Jensen, J., Kaas, A., Brange, J., Whittingham, J.L. and Buschard, K., Sulfatide promotes the folding of proinsulin, preserves insulin crystals, and mediates its monomerization, Glycobiology 11 (2001) 473–479.PubMedGoogle Scholar
  101. Ott, M., Zhivotovsky, B. and Orrenius, S., Role of cardiolipin in cytochrome c release from mitochondria, Cell Death Differ 14 (2007) 1243–1247.PubMedGoogle Scholar
  102. Palsdottir, H. and Hunte, C., Lipids in membrane protein structures, Biochim Biophys Acta 1666 (2004) 2–18.PubMedGoogle Scholar
  103. Papa, S., Lorusso, M. and Di Paola, M., Cooperativity and flexibility of the protonmotive activity of mitochondrial respiratory chain, Biochim Biophys Acta 1757 (2006) 428–436.PubMedGoogle Scholar
  104. Paradies, G., Petrosillo, G. and Ruggiero, F.M., Cardiolipin-dependent decrease of cytochrome c oxidase activity in heart mitochondria from hypothyroid rats, Biochim Biophys Acta 1319 (1997a) 5–8.Google Scholar
  105. Paradies, G., Ruggiero, F.M., Petrosillo, G. and Quagliariello, E., Age-dependent decline in the cytochrome c oxidase activity in rat heart mitochondria: role of cardiolipin, FEBS Lett 406 (1997b) 136–138.Google Scholar
  106. Parekh, V.V., Wilson, M.T. and Van Kaer, L., iNKT-cell responses to glycolipids, Crit Rev Immunol 25 (2005) 183–213.PubMedGoogle Scholar
  107. Park, J.J., Kang, S.J., De Silva, A.D., Stanic, A.K., Casorati, G., Hachey, D.L., Cresswell, P. and Joyce, S., Lipid-protein interactions: biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved, Proc Natl Acad Sci USA 101 (2004) 1022–1026.PubMedGoogle Scholar
  108. Paumard, P., Vaillier, J., Coulary, B., Schaeffer, J., Soubannier, V., Mueller, D.M., Brethes, D., di Rago, J.P. and Velours, J., The ATP synthase is involved in generating mitochondrial cristae morphology, Embo J 21 (2002) 221–230.PubMedGoogle Scholar
  109. Petrosillo, G., Di Venosa, N., Ruggiero, F.M., Pistolese, M., D'Agostino, D., Tiravanti, E., Fiore, T. and Paradies, G., Mitochondrial dysfunction associated with cardiac ischemia/reperfusion can be attenuated by oxygen tension control. Role of oxygen-free radicals and cardiolipin, Biochim Biophys Acta 1710 (2005) 78–86.PubMedGoogle Scholar
  110. Petrosillo, G., Portincasa, P., Grattagliano, I., Casanova, G., Matera, M., Ruggiero, F.M., Ferri, D. and Paradies, G., Mitochondrial dysfunction in rat with nonalcoholic fatty liver Involvement of complex I, reactive oxygen species and cardiolipin, Biochim Biophys Acta 1767 (2007) 1260–1267.PubMedGoogle Scholar
  111. Petrosillo, G., Ruggiero, F.M., Di Venosa, N. and Paradies, G., Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion: role of reactive oxygen species and cardiolipin, Faseb J 17 (2003) 714–716.PubMedGoogle Scholar
  112. Pfeiffer, K., Gohil, V., Stuart, R.A., Hunte, C., Brandt, U., Greenberg, M.L. and Schagger, H., Cardiolipin stabilizes respiratory chain supercomplexes, J Biol Chem 278 (2003) 52873–52880.PubMedGoogle Scholar
  113. Porcelli, S.A., Cutting glycolipids down to size, Nat Immunol 2 (2001) 191–192.PubMedGoogle Scholar
  114. Qin, L., Sharpe, M.A., Garavito, R.M. and Ferguson-Miller, S., Conserved lipid-binding sites in membrane proteins: a focus on cytochrome c oxidase, Curr Opin Struct Biol 17 (2007) 444–450.PubMedGoogle Scholar
  115. Qu, B.H., Strickland, E.H. and Thomas, P.J., Localization and suppression of a kinetic defect in cystic fibrosis transmembrane conductance regulator folding, J Biol Chem 272 (1997) 15739–15744.PubMedGoogle Scholar
  116. Roberts, T.J., Sriram, V., Spence, P.M., Gui, M., Hayakawa, K., Bacik, I., Bennink, J.R., Yewdell, J.W. and Brutkiewicz, R.R., Recycling CD1d1 molecules present endogenous antigens processed in an endocytic compartment to NKT cells, J Immunol 168 (2002) 5409–5414.PubMedGoogle Scholar
  117. Rutz, C., Rosenthal, W. and Schulein, R., A single negatively charged residue affects the orientation of a membrane protein in the inner membrane of Escherichia coli only when it is located adjacent to a transmembrane domain, J Biol Chem 274 (1999) 33757–33763.PubMedGoogle Scholar
  118. Sahin-Toth, M., Kaback, H.R. and Friedlander, M., Association between the amino- and carboxyl-terminal halves of lactose permease is specific and mediated by multiple transmembrane domains, Biochemistry 35 (1996) 2016–2021.PubMedGoogle Scholar
  119. Sambamurti, K., Suram, A., Venugopal, C., Prakasam, A., Zhou, Y., Lahiri, D.K. and Greig, N.H., A partial failure of membrane protein turnover may cause Alzheimer's disease: a new hypothesis, Curr Alzheimer Res 3 (2006) 81–90.PubMedGoogle Scholar
  120. Sanders, C.R. and Myers, J.K., Disease-related misassembly of membrane proteins, Annu Rev Biophys Biomol Struct 33 (2004) 25–51.PubMedGoogle Scholar
  121. Sanghera, N. and Pinheiro, T.J., Binding of prion protein to lipid membranes and implications for prion conversion, J Mol Biol 315 (2002) 1241–1256.PubMedGoogle Scholar
  122. Schafer, E., Dencher, N.A., Vonck, J. and Parcej, D.N., Three-dimensional structure of the respiratory chain supercomplex I1III2IV1 from bovine heart mitochondria, Biochemistry 46 (2007) 12579–12585.PubMedGoogle Scholar
  123. Schagger, H. and Pfeiffer, K., Supercomplexes in the respiratory chains of yeast and mammalian mitochondria, Embo J 19 (2000) 1777–1783.PubMedGoogle Scholar
  124. Schlame, M. and Ren, M., Barth syndrome, a human disorder of cardiolipin metabolism, FEBS Lett 580 (2006) 5450–5455.PubMedGoogle Scholar
  125. Schlame, M., Rua, D. and Greenberg, M.L., The biosynthesis and functional role of cardiolipin, Prog Lipid Res 39 (2000) 257–288.PubMedGoogle Scholar
  126. Schleiff, E., Tien, R., Salomon, M. and Soll, J., Lipid composition of outer leaflet of chloroplast outer envelope determines topology of OEP7, Molecular Biology of the Cell 12 (2001) 4090–4102.PubMedGoogle Scholar
  127. Schmelzer, K., Fahy, E., Subramaniam, S. and Dennis, E.A., The lipid maps initiative in lipidomics, Methods Enzymol 432 (2007) 171–183.PubMedGoogle Scholar
  128. Schmidt, T.R., Jaradat, S.A., Goodman, M., Lomax, M.I. and Grossman, L.I., Molecular evolution of cytochrome c oxidase: rate variation among subunit VIa isoforms, Mol Biol Evol 14 (1997) 595–601.PubMedGoogle Scholar
  129. Scorrano, L., Ashiya, M., Buttle, K., Weiler, S., Oakes, S.A., Mannella, C.A. and Korsmeyer, S.J., A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis, Dev Cell 2 (2002) 55–67.PubMedGoogle Scholar
  130. Sedlak, E., Panda, M., Dale, M.P., Weintraub, S.T. and Robinson, N.C., Photolabeling of cardiolipin binding subunits within bovine heart cytochrome c oxidase, Biochemistry 45 (2006) 746–754.PubMedGoogle Scholar
  131. Shinzawa-Itoh, K., Aoyama, H., Muramoto, K., Terada, H., Kurauchi, T., Tadehara, Y., Yamasaki, A., Sugimura, T., Kurono, S., Tsujimoto, K., Mizushima, T., Yamashita, E., Tsukihara, T. and Yoshikawa, S., Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidase, Embo J 26 (2007) 1713–1725.PubMedGoogle Scholar
  132. Skach, W.R., Calayag, M.C. and Lingappa, V.R., Evidence for an alternate model of human P-glycoprotein structure and biogenesis, J Biol Chem 268 (1993) 6903–6908.PubMedGoogle Scholar
  133. Sun, J., Wu, J., Carrasco, N. and Kaback, H.R., Identification of the epitope for monoclonal antibody 4B1 which uncouples lactose and proton translocation in the lactose permease of Escherichia coli, Biochemistry 35 (1996) 990–998.PubMedGoogle Scholar
  134. Taanman, J.W. and Capaldi, R.A., Subunit VIa of yeast cytochrome c oxidase is not necessary for assembly of the enzyme complex but modulates the enzyme activity. Isolation and characterization of the nuclear-coded gene, J Biol Chem 268 (1993) 18754–18761.PubMedGoogle Scholar
  135. van Klompenburg, W., Nilsson, I., von Heijne, G. and de Kruijff, B., Anionic phospholipids are determinants of membrane protein topology, Embo J 16 (1997) 4261–4266.PubMedGoogle Scholar
  136. van Meer, G., Leeflang, B.R., Liebisch, G., Schmitz, G. and Goni, F.M., The European lipidomics initiative: enabling technologies, Methods Enzymol 432 (2007) 213–232.PubMedGoogle Scholar
  137. Vigh, L., Escriba, P.V., Sonnleitner, A., Sonnleitner, M., Piotto, S., Maresca, B., Horvath, I. and Harwood, J.L., The significance of lipid composition for membrane activity: new concepts and ways of assessing function, Prog Lipid Res 44 (2005) 303–344.PubMedGoogle Scholar
  138. Vogel, F., Bornhovd, C., Neupert, W. and Reichert, A.S., Dynamic subcompartmentalization of the mitochondrial inner membrane, J Cell Biol 175 (2006) 237–247.PubMedGoogle Scholar
  139. von Heijne, G., The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology, Embo J 5 (1986) 3021–3027.PubMedGoogle Scholar
  140. von Heijne, G., Control of topology and mode of assembly of a polytopic membrane protein by positively charged residues, Nature 341 (1989) 456–458.Google Scholar
  141. Wang, X., Bogdanov, M. and Dowhan, W., Topology of polytopic membrane protein subdomains is dictated by membrane phospholipid composition, Embo J 21 (2002) 5673–5681.PubMedGoogle Scholar
  142. White, S.H. and von Heijne, G., Do protein-lipid interactions determine the recognition of transmembrane helices at the ER translocon?, Biochem Soc Trans 33 (2005) 1012–1015.PubMedGoogle Scholar
  143. Xia, D., Esser, L., Yu, L. and Yu, C.A., Structural basis for the mechanism of electron bifurcation at the quinol oxidation site of the cytochrome bc1 complex, Photosynth Res 92 (2007) 17–34.PubMedGoogle Scholar
  144. Xie, J., Bogdanov, M., Heacock, P. and Dowhan, W., Phosphatidylethanolamine and monoglucosyldiacylglycerol are interchangeable in supporting topogenesis and function of the polytopic membrane protein lactose permease, J Biol Chem 281 (2006) 19172–19178.PubMedGoogle Scholar
  145. Xie, J., Bogdanov, M., Heacock, P. and Dowhan, W., To flip or not to flip: protein – lipid charge interactions are determinants of transmembrane domain orientation, J Biol Chem (2008) submitted.Google Scholar
  146. Xu, Y., Malhotra, A., Ren, M. and Schlame, M., The enzymatic function of tafazzin, J Biol Chem 281 (2006) 39217–39224.PubMedGoogle Scholar
  147. Yanagisawa, K., GM1 ganglioside and the seeding of amyloid in Alzheimer's disease: endogenous seed for Alzheimer amyloid, Neuroscientist 11 (2005) 250–260.PubMedGoogle Scholar
  148. Yanagisawa, K., Odaka, A., Suzuki, N. and Ihara, Y., GM1 ganglioside-bound amyloid beta-protein (A beta): a possible form of preamyloid in Alzheimer's disease, Nat Med 1 (1995) 1062–1066.PubMedGoogle Scholar
  149. Yankovskaya, V., Horsefield, R., Tornroth, S., Luna-Chavez, C., Miyoshi, H., Leger, C., Byrne, B., Cecchini, G. and Iwata, S., Architecture of succinate dehydrogenase and reactive oxygen species generation, Science 299 (2003) 700–704.PubMedGoogle Scholar
  150. Zhang, J.T., Sequence requirements for membrane assembly of polytopic membrane proteins: molecular dissection of the membrane insertion process and topogenesis of the human MDR3 P-glycoprotein, Mol Biol Cell 7 (1996) 1709–1721.PubMedGoogle Scholar
  151. Zhang, J.T., The multi-structural feature of the multidrug resistance gene product P-glycoprotein: implications for its mechanism of action (hypothesis), Mol Membr Biol 18 (2001) 145–152.PubMedGoogle Scholar
  152. Zhang, J.T., Lee, C.H., Duthie, M. and Ling, V., Topological determinants of internal transmembrane segments in P-glycoprotein sequences, J Biol Chem 270 (1995) 1742–1746.PubMedGoogle Scholar
  153. Zhang, J.T. and Ling, V., Study of membrane orientation and glycosylated extracellular loops of mouse P-glycoprotein by in vitro translation, J Biol Chem 266 (1991) 18224–18232.PubMedGoogle Scholar
  154. Zhang, M., Mileykovskaya, E. and Dowhan, W., Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane, J Biol Chem 277 (2002) 43553–43556.PubMedGoogle Scholar
  155. Zhang, M., Mileykovskaya, E. and Dowhan, W., Cardiolipin is essential for organization of complexes III and IV into a supercomplex in intact yeast mitochondria, J Biol Chem 280 (2005a) 29403–29408.Google Scholar
  156. Zhang, W., Bogdanov, M., Pi, J., Pittard, A.J. and Dowhan, W., Reversible topological organization within a polytopic membrane protein is governed by a change in membrane phospholipid composition, J Biol Chem 278 (2003) 50128–50135.PubMedGoogle Scholar
  157. Zhang, W., Campbell, H.A., King, S.C. and Dowhan, W., Phospholipids as determinants of membrane protein topology. Phosphatidylethanolamine is required for the proper topological organization of the gamma-aminobutyric acid permease (GabP) of Escherichia coli, J Biol Chem 280 (2005b) 26032–26038.Google Scholar
  158. Zhao, H., Przybylska, M., Wu, I.H., Zhang, J., Siegel, C., Komarnitsky, S., Yew, N.S. and Cheng, S.H., Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes, Diabetes 56 (2007) 1210–1218.PubMedGoogle Scholar
  159. Zhu, Q., von Dippe, P., Xing, W. and Levy, D., Membrane topology and cell surface targeting of microsomal epoxide hydrolase. Evidence for multiple topological orientations, J Biol Chem 274 (1999) 27898–27904.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Mikhail Bogdanov
  • Eugenia Mileykovskaya
  • William Dowhan
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Texas-Houston, Medical School, 6431 Fannin StUSA

Personalised recommendations