Metabolism of very long-chain fatty acids: Genes and pathophysiology

Biomolecules and Therapeutics

Volumn 22, Issue 2, 2014, Pages 83-92

  Sassa, Takayuki ^a   Kihara, Akio ^a  

^a HOKKAIDO UNIVERSITY   (Japan)

Author keywords

Ceramide; Elovl; Glycerophospholipids; Ichthyosis; Leukodystrophy; Sphingolipids

Indexed keywords

3 HYDROXYACYL COENZYME A DEHYDROGENASE; ACETYL COENZYME A ACYLTRANSFERASE; ACYL COENZYME A; DOCOSAHEXAENOIC ACID; ISOENZYME; LIPID; MALONYL COENZYME A; MYELIN; SPHINGOLIPID; VERY LONG CHAIN FATTY ACID;

ABCA12 GENE; ABCD1 GENE; ACOX1 GENE; ADRENOLEUKODYSTROPHY; BRAIN TISSUE; CERS3 GENE; ELOVL4 GENE; ENZYME MECHANISM; ENZYME SPECIFICITY; EPIDERMIS CELL; FA2H GENE; FATTY ACID METABOLISM; FATTY ACID SYNTHESIS; GENE MUTATION; HACD1 GENE; HSD17BETA4 GENE; HUMAN; LEUKODYSTROPHY; MAMMAL; MOLECULAR GENETICS; MOLECULAR PATHOLOGY; MUTATIONAL ANALYSIS; MYOPATHY; NONHUMAN; PERMEABILITY BARRIER; RETINA; REVIEW; SPASTIC PARAPLEGIA; STARGARDT DISEASE; TER GENE; TESTIS; TISSUE DISTRIBUTION; TRANSCRIPTION ELONGATION; X LINKED ICHTHYOSIS;

EID: 84897066334     PISSN: 19769148     EISSN: 20054483     Source Type: Journal    
DOI: 10.4062/biomolther.2014.017     Document Type: Review

References (95)

1. Abe, K., Ohno, Y., Sassa, T., Taguchi, R., Çalişkan, M., Ober, C. and Kihara, A. (2013) Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profle. J. Biol. Chem. 288, 36741-36749.
2. Agbaga, M. P., Mandal, M. N. and Anderson, R. E. (2010) Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein. J. Lipid Res. 51, 1624-1642.
3. Akiyama, M. (2014) The roles of ABCA12 in epidermal lipid barrier formation and keratinocyte differentiation. Biochim. Biophys. Acta 1841, 435-440.
4. Akiyama, M., Sugiyama-Nakagiri, Y., Sakai, K., McMillan, J. R., Goto, M., Arita, K., Tsuji-Abe, Y., Tabata, N., Matsuoka, K., Sasaki, R., Sawamura, D. and Shimizu, H. (2005) Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. J. Clin. Invest. 115, 1777-1784.
5. Aldahmesh, M. A., Mohamed, J. Y., Alkuraya, H. S., Verma, I. C., Puri, R. D., Alaiya, A. A., Rizzo, W. B. and Alkuraya, F. S. (2011) Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. Am. J. Hum. Genet. 89, 745-750.
6. Alderson, N. L., Maldonado, E. N., Kern, M. J., Bhat, N. R. and Hama, H. (2006) FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain. J. Lipid Res. 47, 2772-2780.
7. Aveldaño, M. I. and Sprecher, H. (1987) Very long chain (C24 to C36) polyenoic fatty acids of the n-3 and n-6 series in dipolyunsaturated phosphatidylcholines from bovine retina. J. Biol. Chem. 262, 1180-1186.
8. Bannenberg, G. and Serhan, C. N. (2010) Specialized pro-resolving lipid mediators in the infammatory response: An update. Biochim. Biophys. Acta 1801, 1260-1273.
9. Bazan, N. G., Calandria, J. M. and Serhan, C. N. (2010) Rescue and repair during photoreceptor cell renewal mediated by docosa-hexaenoic acid-derived neuroprotectin D1. J. Lipid Res. 51, 2018-2031.
10. Becker, I., Wang-Eckhardt, L., Yaghootfam, A., Gieselmann, V. and Eckhardt, M. (2008) Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specifc expression of CerS2/Lass2. Histochem. Cell Biol. 129, 233-241.
11. Berger, J., Pujol, A., Aubourg, P. and Forss-Petter, S. (2010) Current and future pharmacological treatment strategies in X-linked adre-noleukodystrophy. Brain Pathol. 20, 845-856.
12. Breiden, B. and Sandhoff, K. (2014) The role of sphingolipid metabolism in cutaneous permeability barrier formation. Biochim. Biophys. Acta 1841, 441-452.
13. Butovich, I. A. (2010) Fatty acid composition of cholesteryl esters of human meibomian gland secretions. Steroids 75, 726-733.
14. Butovich, I. A. (2013) Tear flm lipids. Exp. Eye Res. 117, 4-27.
15. Butovich, I. A., Wojtowicz, J. C. and Molai, M. (2009) Human tear flm and meibum. Very long chain wax esters and (O-acyl)-omega-hy-droxy fatty acids of meibum. J. Lipid Res. 50, 2471-2485.
16. Çalişkan, M., Chong, J. X., Uricchio, L., Anderson, R., Chen, P., So-ugnez, C., Garimella, K., Gabriel, S. B., dePristo, M. A., Shakir, K., Matern, D., Das, S., Waggoner, D., Nicolae, D. L. and Ober, C. (2011) Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13. Hum. Mol. Genet. 20, 1285-1289.
17. Donoso, L. A., Edwards, A. O., Frost, A., Vrabec, T., Stone, E. M., Ha-geman, G. S. and Perski, T. (2001) Autosomal dominant Stargardt-like macular dystrophy. Surv. Ophthalmol. 46, 149-163.
18. Eckl, K. M., Tidhar, R., Thiele, H., Oji, V., Hausser, I., Brodesser, S., Preil, M. L., Önal-Akan, A., Stock, F., Müller, D., Becker, K., Casper, R., Nürnberg, G., Altmüller, J., Nürnberg, P., Traupe, H., Futerman, A. H. and Hennies, H. C. (2013) Impaired epidermal ceramide synthesis causes autosomal recessive congenital ichthyosis and reveals the importance of ceramide acyl chain length. J. Invest. Dermatol. 133, 2202-2211.
19. Edvardson, S., Hama, H., Shaag, A., Gomori, J. M., Berger, I., Soffer, D., Korman, S. H., Taustein, I., Saada, A. and Elpeleg, O. (2008) Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. Am. J. Hum. Genet. 83, 643-648.
20. Ejsing, C. S., Sampaio, J. L., Surendranath, V., Duchoslav, E., Ekroos, K., Klemm, R. W., Simons, K. and Shevchenko, A. (2009) Global analysis of the yeast lipidome by quantitative shotgun mass spec-trometry. Proc. Natl. Acad. Sci. U.S.A. 106, 2136-2141.
21. Elias, P. M., Williams, M. L. and Feingold, K. R. (2012) Abnormal barrier function in the pathogenesis of ichthyosis: therapeutic implications for lipid metabolic disorders. Clin. Dermatol. 30, 311-322.
22. Engelen, M., Tran, L., Ofman, R., Brennecke, J., Moser, A. B., Dijkstra, I. M., Wanders, R. J., Poll-The, B. T. and Kemp, S. (2012) Bezaf-brate for X-linked adrenoleukodystrophy. PLoS One 7, e41013.
23. Furland, N. E., Oresti, G. M., Antollini, S. S., Venturino, A., Maldonado, E. N. and Aveldaño, M. I. (2007a) Very long-chain polyunsaturated fatty acids are the major acyl groups of sphingomyelins and ce-ramides in the head of mammalian spermatozoa. J. Biol. Chem. 282, 18151-18161.
24. Furland, N. E., Zanetti, S. R., Oresti, G. M., Maldonado, E. N. and Aveldaño, M. I. (2007b) Ceramides and sphingomyelins with high proportions of very long-chain polyunsaturated fatty acids in mammalian germ cells. J. Biol. Chem. 282, 18141-18150.
25. Ginkel, C., Hartmann, D., vom Dorp, K., Zlomuzica, A., Farwanah, H., Eckhardt, M., Sandhoff, R., Degen, J., Rabionet, M., Dere, E., Dör-mann, P., Sandhoff, K. and Willecke, K. (2012) Ablation of neuronal ceramide synthase 1 in mice decreases ganglioside levels and expression of myelin-associated glycoprotein in oligodendrocytes. J. Biol. Chem. 287, 41888-41902.
26. Guillou, H., Zadravec, D., Martin, P. G. and Jacobsson, A. (2010) The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice. Prog. Lipid Res. 49, 186-199.
27. Hama, H. (2010) Fatty acid 2-Hydroxylation in mammalian sphingo-lipid biology. Biochim. Biophys. Acta 1801, 405-414.
28. Harkewicz, R., Du, H., Tong, Z., Alkuraya, H., Bedell, M., Sun, W., Wang, X., Hsu, Y. H., Esteve-Rudd, J., Hughes, G., Su, Z., Zhang, M., Lopes, V. S., Molday, R. S., Williams, D. S., Dennis, E. A. and Zhang, K. (2012) Essential role of ELOVL4 protein in very long chain fatty acid synthesis and retinal function. J. Biol. Chem. 287, 11469-11480.
29. Ikeda, M., Kanao, Y., Yamanaka, M., Sakuraba, H., Mizutani, Y., Iga-rashi, Y. and Kihara, A. (2008) Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis. FEBS Lett. 582, 2435-2440.
30. Imgrund, S., Hartmann, D., Farwanah, H., Eckhardt, M., Sandhoff, R., Degen, J., Gieselmann, V., Sandhoff, K. and Willecke, K. (2009) Adult ceramide synthase 2 (CERS2)-defcient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas. J. Biol. Chem. 284, 33549-33560.
31. Iwabuchi, K., Prinetti, A., Sonnino, S., Mauri, L., Kobayashi, T., Ishii, K., Kaga, N., Murayama, K., Kurihara, H., Nakayama, H., Yoshizaki, F., Takamori, K., Ogawa, H. and Nagaoka, I. (2008) Involvement of very long fatty acid-containing lactosylceramide in lactosylcera-mide-mediated superoxide generation and migration in neutro-phils. Glycoconj. J. 25, 357-374.
32. Jakobsson, A., Westerberg, R. and Jacobsson, A. (2006) Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog. Lipid Res. 45, 237-249.
33. Jennemann, R., Rabionet, M., Gorgas, K., Epstein, S., Dalpke, A., Ro-thermel, U., Bayerle, A., van der Hoeven, F., Imgrund, S., Kirsch, J., Nickel, W., Willecke, K., Riezman, H., Gröne, H. J. and Sand-hoff, R. (2012) Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum. Mol. Genet. 21, 586-608.
34. Karan, G., Yang, Z., Howes, K., Zhao, Y., Chen, Y., Cameron, D. J., Lin, Y., Pearson, E. and Zhang, K. (2005) Loss of ER retention and sequestration of the wild-type ELOVL4 by Stargardt disease dominant negative mutants. Mol. Vis. 11, 657-664.
35. Kasahara, K. and Sanai, Y. (2000) Functional roles of glycosphingolip-ids in signal transduction via lipid rafts. Glycoconj. J. 17, 153-162.
36. Kemp, S., Berger, J. and Aubourg, P. (2012) X-linked adrenoleuko-dystrophy: Clinical, metabolic, genetic and pathophysiological aspects. Biochim. Biophys. Acta 1822, 1465-1474.
37. Korb, D. R. and Blackie, C. A. (2008) Meibomian gland diagnostic ex-pressibility: correlation with dry eye symptoms and gland location. Cornea 27, 1142-1147.
38. Li, D., Gonzalez, O., Bachinski, L. L. and Roberts, R. (2000) Human protein tyrosine phosphatase-like gene: expression profle, genom-ic structure, and mutation analysis in families with ARVD. Gene 256, 237-243.
39. Li, W., Sandhoff, R., Kono, M., Zerfas, P., Hoffmann, V., Ding, B. C., Proia, R. L. and Deng, C. X. (2007) Depletion of ceramides with very long chain fatty acids causes defective skin permeability barrier function, and neonatal lethality in ELOVL4 defcient mice. Int. J. Biol. Sci. 3, 120-128.
40. Lin, D. S., Connor, W. E., Wolf, D. P., Neuringer, M. and Hachey, D. L. (1993) Unique lipids of primate spermatozoa: desmosterol and docosahexaenoic acid. J. Lipid Res. 34, 491-499.
41. Masukawa, Y., Narita, H., Shimizu, E., Kondo, N., Sugai, Y., Oba, T., Homma, R., Ishikawa, J., Takagi, Y., Kitahara, T., Takema, Y. and Kita, K. (2008) Characterization of overall ceramide species in human stratum corneum. J. Lipid Res. 49, 1466-1476.
42. Matsuzaka, T., Shimano, H., Yahagi, N., Kato, T., Atsumi, A., Yama-moto, T., Inoue, N., Ishikawa, M., Okada, S., Ishigaki, N., Iwasaki, H., Iwasaki, Y., Karasawa, T., Kumadaki, S., Matsui, T., Sekiya, M., Ohashi, K., Hasty, A. H., Nakagawa, Y., Takahashi, A., Suzuki, H., Yatoh, S., Sone, H., Toyoshima, H., Osuga, J. and Yamada, N. (2007) Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nat. Med. 13, 1193-1202.
43. Mizutani, Y., Kihara, A., Chiba, H., Tojo, H. and Igarashi, Y. (2008) 2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length. J. Lipid Res. 49, 2356-2364.
44. Mizutani, Y., Mitsutake, S., Tsuji, K., Kihara, A. and Igarashi, Y. (2009) Ceramide biosynthesis in keratinocyte and its role in skin function. Biochimie 91, 784-790.
45. Mizutani, Y., Sun, H., Ohno, Y., Sassa, T., Wakashima, T., Obara, M., Yuyama, K., Kihara, A. and Igarashi, Y. (2013) Cooperative synthesis of ultra long-chain fatty acid and ceramide during keratinocyte differentiation. PLoS One 8, e67317.
46. Moon, Y. A., Hammer, R. E. and Horton, J. D. (2009) Deletion of ELOVL5 leads to fatty liver through activation of SREBP-1c in mice. J. Lipid Res. 50, 412-423.
47. Moon, Y. A. and Horton, J. D. (2003) Identifcation of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade. J. Biol. Chem. 278, 7335-7343.
48. Moon, Y. A., Shah, N. A., Mohapatra, S., Warrington, J. A. and Hor-ton, J. D. (2001) Identifcation of a mammalian long chain fatty acyl elongase regulated by sterol regulatory element-binding proteins. J. Biol. Chem. 276, 45358-45366.
49. Morita, M. and Imanaka, T. (2012) Peroxisomal ABC transporters: structure, function and role in disease. Biochim. Biophys. Acta 1822, 1387-1396.
50. Morrow, M. R., Singh, D., Lu, D. and Grant, C. W. (1995) Glycosphin-golipid fatty acid arrangement in phospholipid bilayers: cholesterol effects. Biophys. J. 68, 179-186.
51. Mosser, J., Douar, A. M., Sarde, C. O., Kioschis, P., Feil, R., Moser, H., Poustka, A. M., Mandel, J. L. and Aubourg, P. (1993) Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 361, 726-730.
52. Muhammad, E., Reish, O., Ohno, Y., Scheetz, T., DeLuca, A., Searby, C., Regev, M., Benyamini, L., Fellig, Y., Kihara, A., Sheffeld, V. C. and Parvari, R. (2013) Congenital myopathy is caused by mutation of HACD1. Hum. Mol. Genet. 22, 5229-5236.
53. Mukherjee, P. K., Marcheselli, V. L., de Rivero Vaccari, J. C., Gordon, W. C., Jackson, F. E. and Bazan, N. G. (2007) Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apop-tosis with concomitant neuroprotectin D1 synthesis. Proc. Natl. Acad. Sci. U.S.A. 104, 13158-13163.
54. Naganuma, T., Sato, Y., Sassa, T., Ohno, Y. and Kihara, A. (2011) Biochemical characterization of the very long-chain fatty acid elon-gase ELOVL7. FEBS Lett. 585, 3337-3341.
55. Obara, K., Kojima, R. and Kihara, A. (2013) Effects on vesicular transport pathways at the late endosome in cells with limited very long-chain fatty acids. J. Lipid Res. 54, 831-842.
56. Ofman, R., Dijkstra, I. M., van Roermund, C. W., Burger, N., Turken-burg, M., van Cruchten, A., van Engen, C. E., Wanders, R. J. and Kemp, S. (2010) The role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy. EMBO Mol. Med. 2, 90-97.
57. Ohashi, Y., Dogru, M. and Tsubota, K. (2006) Laboratory fndings in tear fuid analysis. Clin. Chim. Acta 369, 17-28.
58. Ohno, Y., Suto, S., Yamanaka, M., Mizutani, Y., Mitsutake, S., Igarashi, Y., Sassa, T. and Kihara, A. (2010) ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis. Proc. Natl. Acad. Sci. U.S.A. 107, 18439-18444.
59. Oji, V., Tadini, G., Akiyama, M., Blanchet Bardon, C., Bodemer, C., Bourrat, E., Coudiere, P., DiGiovanna, J. J., Elias, P., Fischer, J., Fleckman, P., Gina, M., Harper, J., Hashimoto, T., Hausser, I., Hen-nies, H. C., Hohl, D., Hovnanian, A., Ishida-Yamamoto, A., Jacyk, W. K., Leachman, S., Leigh, I., Mazereeuw-Hautier, J., Milstone, L., Morice-Picard, F., Paller, A. S., Richard, G., Schmuth, M., Shimizu, H., Sprecher, E., Van Steensel, M., Taïeb, A., Toro, J. R., Vabres, P., Vahlquist, A., Williams, M. and Traupe, H. (2010) Revised nomenclature and classifcation of inherited ichthyoses: results of the frst ichthyosis consensus conference in sorèze 2009. J. Am. Acad. Dermatol. 63, 607-641.
60. Okuda, A., Naganuma, T., Ohno, Y., Abe, K., Yamagata, M., Igarashi, Y. and Kihara, A. (2010) Hetero-oligomeric interactions of an ELOVL4 mutant protein: implications in the molecular mechanism of Stargardt-3 macular dystrophy. Mol. Vis. 16, 2438-2445.
61. Paintlia, A. S., Gilg, A. G., Khan, M., Singh, A. K., Barbosa, E. and Singh, I. (2003) Correlation of very long chain fatty acid accumulation and infammatory disease progression in childhood X-ALD: implications for potential therapies. Neurobiol. Dis. 14, 425-439.
62. Pelé, M., Tiret, L., Kessler, J. L., Blot, S. and Panthier, J. J. (2005) SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronucle-ar myopathy in dogs. Hum. Mol. Genet. 14, 1417-1427.
63. Pewzner-Jung, Y., Brenner, O., Braun, S., Laviad, E. L., Ben-Dor, S., Feldmesser, E., Horn-Saban, S., Amann-Zalcenstein, D., Raanan, C., Berkutzki, T., Erez-Roman, R., Ben-David, O., Levy, M., Holz-man, D., Park, H., Nyska, A., Merrill, A. H., Jr. and Futerman, A. H. (2010a) A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy. J. Biol. Chem. 285, 10911-10923.
64. Pewzner-Jung, Y., Park, H., Laviad, E. L., Silva, L. C., Lahiri, S., Stiban, J., Erez-Roman, R., Brügger, B., Sachsenheimer, T., Wieland, F., Prieto, M., Merrill, A. H., Jr. and Futerman, A. H. (2010b) A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways. J. Biol. Chem. 285, 10902-10910.
65. Poll-The, B. T., Roels, F., Ogier, H., Scotto, J., Vamecq, J., Schutgens, R. B., Wanders, R. J., van Roermund, C. W., van Wijland, M. J., Schram, A. W., Tagar, J. M. and Saudubray J. M. (1988) A new peroxisomal disorder with enlarged peroxisomes and a specifc defciency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodys-trophy). Am. J. Hum. Genet. 42, 422-434.
66. Poulos, A., Sharp, P., Johnson, D. and Easton, C. (1988) The occurrence of polyenoic very long chain fatty acids with greater than 32 carbon atoms in molecular species of phosphatidylcholine in normal and peroxisome-defcient (Zellweger's syndrome) brain. Biochem. J. 253, 645-650.
67. Proksch, E., Brandner, J. M. and Jensen, J. M. (2008) The skin: an indispensable barrier. Exp. Dermatol. 17, 1063-1072.
68. Prottey, C. (1977) Investigation of functions of essential fatty acids in the skin. Br. J. Dermatol. 97, 29-38.
69. Rabionet, M., Gorgas, K. and Sandhoff, R. (2014) Ceramide synthesis in the epidermis. Biochim. Biophys. Acta 1841, 422-434.
70. Rabionet, M., van der Spoel, A. C., Chuang, C. C., von Tümpling-Ra-dosta, B., Litjens, M., Bouwmeester, D., Hellbusch, C. C., Körner, C., Wiegandt, H., Gorgas, K., Platt, F. M., Gröne, H. J. and Sand-hoff, R. (2008) Male germ cells require polyenoic sphingolipids with complex glycosylation for completion of meiosis: a link to ceramide synthase-3. J. Biol. Chem. 283, 13357-13369.
71. Radner, F. P., Marrakchi, S., Kirchmeier, P., Kim, G. J., Ribierre, F., Ka-moun, B., Abid, L., Leipoldt, M., Turki, H., Schempp, W., Heilig, R., Lathrop, M. and Fischer, J. (2013) Mutations in CERS3 cause au-tosomal recessive congenital ichthyosis in humans. PLoS Genet. 9, e1003536.
72. Rizzo, W. B., Leshner, R. T., Odone, A., Dammann, A. L., Craft, D. A., Jensen, M. E., Jennings, S. S., Davis, S., Jaitly, R. and Sgro J. A. (1989) Dietary erucic acid therapy for X-linked adrenoleukodystro-phy. Neurology 39, 1415-1422.
73. Robinson, B. S., Johnson, D. W. and Poulos, A. (1990) Unique molecular species of phosphatidylcholine containing very-long-chain (C24-C38) polyenoic fatty acids in rat brain. Biochem. J. 265, 763-767.
74. Sandhoff, R., Geyer, R., Jennemann, R., Paret, C., Kiss, E., Yamashi-ta, T., Gorgas, K., Sijmonsma, T. P., Iwamori, M., Finaz, C., Proia, R. L., Wiegandt, H. and Gröne, H. J. (2005) Novel class of glyco-sphingolipids involved in male fertility. J. Biol. Chem. 280, 27310-27318.
75. SanGiovanni, J. P. and Chew, E. Y. (2005) The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog. Retin. Eye Res. 24, 87-138.
76. Sassa, T., Ohno, Y., Suzuki, S., Nomura, T., Nishioka, C., Kashiwagi, T., Hirayama, T., Akiyama, M., Taguchi, R., Shimizu, H., Itohara, S. and Kihara, A. (2013) Impaired epidermal permeability barrier in mice lacking Elovl1, the gene responsible for very-long-chain fatty acid production. Mol. Cell. Biol. 33, 2787-2796.
77. Sassa, T., Suto, S., Okayasu, Y. and Kihara, A. (2012) A shift in sphin-golipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells. Biochim. Biophys. Acta 1821, 1031-1037.
78. Sassa, T., Wakashima, T., Ohno, Y. and Kihara, A. (2014) Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid. J. Lipid Res., 55, 524-530.
79. Sastry, P. S. (1985) Lipids of nervous tissue: composition and metabolism. Prog. Lipid Res. 24, 69-176.
80. Silva, L. C., Ben David, O., Pewzner-Jung, Y., Laviad, E. L., Stiban, J., Bandyopadhyay, S., Merrill, A. H., Jr., Prieto, M. and Futerman, A. H. (2012) Ablation of ceramide synthase 2 strongly affects biophysical properties of membranes. J. Lipid Res. 53, 430-436.
81. Simons, K. and Ikonen, E. (1997) Functional rafts in cell membranes. Nature 387, 569-572.
82. Sonnino, S., Prinetti, A., Nakayama, H., Yangida, M., Ogawa, H. and Iwabuchi, K. (2009) Role of very long fatty acid-containing glyco-sphingolipids in membrane organization and cell signaling: the model of lactosylceramide in neutrophils. Glycoconj. J. 26, 615-621.
83. t'Kindt, R., Jorge, L., Dumont, E., Couturon, P., David, F., Sandra, P. and Sandra, K. (2012) Profling and characterizing skin ceramides using reversed-phase liquid chromatography-quadrupole time-of-fight mass spectrometry. Anal. Chem. 84, 403-411.
84. Tidhar, R. and Futerman, A. H. (2013) The complexity of sphingolipid biosynthesis in the endoplasmic reticulum. Biochim. Biophys. Acta 1833, 2511-2518.
85. Uauy, R., Hoffman, D. R., Peirano, P., Birch, D. G. and Birch, E. E. (2001) Essential fatty acids in visual and brain development. Lipids 36, 885-895.
86. van Roermund, C. W., Visser, W. F., Ijlst, L., van Cruchten, A., Boek, M., Kulik, W., Waterham, H. R. and Wanders, R. J. (2008) The human peroxisomal ABC half transporter ALDP functions as a ho-modimer and accepts acyl-CoA esters. FASEB J. 22, 4201-4208.
87. Vasireddy, V., Jablonski, M. M., Mandal, M. N., Raz-Prag, D., Wang, X. F., Nizol, L., Iannaccone, A., Musch, D. C., Bush, R. A., Salem, N., Jr., Sieving, P. A. and Ayyagari, R. (2006) Elovl4 5-bp-deletion knock-in mice develop progressive photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 47, 4558-4568.
88. Vasireddy, V., Uchida, Y., Salem, N., Jr., Kim, S. Y., Mandal, M. N., Reddy, G. B., Bodepudi, R., Alderson, N. L., Brown, J. C., Hama, H., Dlugosz, A., Elias, P. M., Holleran, W. M. and Ayyagari, R. (2007) Loss of functional ELOVL4 depletes very long-chain fatty acids (≥C28) and the unique ω-O-acylceramides in skin leading to neonatal death. Hum. Mol. Genet. 16, 471-482.
89. Vasireddy, V., Wong, P. and Ayyagari, R. (2010) Genetics and molecular pathology of Stargardt-like macular degeneration. Prog. Retin. Eye Res. 29, 191-207.
90. Wanders, R. J. (2014) Metabolic functions of peroxisomes in health and disease. Biochimie 98, 36-44.
91. Watkins, P. A., McGuinness, M. C., Raymond, G. V., Hicks, B. A., Sisk, J. M., Moser, A. B. and Moser, H. W. (1995) Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase defcien-cies. Ann. Neurol. 38, 472-477.
92. Westerberg, R., Tvrdik, P., Undén, A. B., Månsson, J. E., Norlén, L., Jakobsson, A., Holleran, W. H., Elias, P. M., Asadi, A., Flodby, P., Toftgård, R., Capecchi, M. R. and Jacobsson, A. (2004) Role for ELOVL3 and fatty acid chain length in development of hair and skin function. J. Biol. Chem. 279, 5621-5629.
93. Yamanaka, W. K., Clemans, G. W. and Hutchinson, M. L. (1980) Essential fatty acids defciency in humans. Prog. Lipid Res. 19, 187-215.
94. Zadravec, D., Tvrdik, P., Guillou, H., Haslam, R., Kobayashi, T., Napier, J. A., Capecchi, M. R. and Jacobsson, A. (2011) ELOVL2 controls the level of n-6 28:5 and 30:5 fatty acids in testis, a prerequisite for male fertility and sperm maturation in mice. J. Lipid Res. 52, 245-255.
95. Zhang, K., Kniazeva, M., Han, M., Li, W., Yu, Z., Yang, Z., Li, Y., Metz-ker, M. L., Allikmets, R., Zack, D. J., Kakuk, L. E., Lagali, P. S., Wong, P. W., MacDonald, I. M., Sieving, P. A., Figueroa, D. J., Austin, C. P., Gould, R. J., Ayyagari, R. and Petrukhin, K. (2001) A 5-bp deletion in ELOVL4 is associated with two related forms of autoso-mal dominant macular dystrophy. Nat. Genet. 27, 89-93.