title: Very-long-chain polyunsaturated fatty acids accumulate in phosphatidylcholine of fibroblasts from patients with Zellweger syndrome and acyl-CoA oxidase1 deficiency.
abstract: Peroxisomes are subcellular organelles that function in multiple anabolic and catabolic processes, including β-oxidation of very-long-chain fatty acids (VLCFA) and biosynthesis of ether phospholipids. Peroxisomal disorders caused by defects in peroxisome biogenesis or peroxisomal β-oxidation manifest as severe neural disorders of the central nervous system. Abnormal peroxisomal metabolism is thought to be responsible for the clinical symptoms of these diseases, but their molecular pathogenesis remains to be elucidated. We performed lipidomic analysis to identify aberrant metabolites in fibroblasts from patients with Zellweger syndrome (ZS), acyl-CoA oxidase1 (AOx) deficiency, D-bifunctional protein (D-BP) and X-linked adrenoleukodystrophy (X-ALD), as well as in peroxisome-deficient Chinese hamster ovary cell mutants. In cells deficient in peroxisomal biogenesis, plasmenylethanolamine was remarkably reduced and phosphatidylethanolamine was increased. Marked accumulation of very-long-chain saturated fatty acid and monounsaturated fatty acids in phosphatidylcholine was observed in all mutant cells. Very-long-chain polyunsaturated fatty acid (VLC-PUFA) levels were significantly elevated, whilst phospholipids containing docosahexaenoic acid (DHA, C22:6n-3) were reduced in fibroblasts from patients with ZS, AOx deficiency, and D-BP deficiency, but not in fibroblasts from an X-ALD patient. Because patients with AOx deficiency suffer from more severe symptoms than those with X-ALD, accumulation of VLC-PUFA and/or reduction of DHA may be associated with the severity of peroxisomal diseases.
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka 812-8581, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka 812-8581, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Honsho
authors.affiliation: Department of Medical Biology, Akita University Graduate School of Medicine, Akita 010-8502, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka 812-8581, Japan. Electronic address: yfujiki@kyudai.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiki
mesh_terms: D000214:Acyl Coenzyme A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D018901:Peroxisomal Disorders / Q000378:metabolism / Q000473:pathology; D020675:Peroxisomes / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D015211:Zellweger Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000214:Acyl Coenzyme A; D005231:Fatty Acids, Unsaturated; D010713:Phosphatidylcholines
keywords: Lipidomics; Peroxisomal β-oxidation; Peroxisome; Very-long-chain fatty acid; X-ALD; Zellweger syndrome