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Functional characterisation of peroxisomal β‐oxidation disorders in fibroblasts using lipidomics
Author(s) -
Herzog Katharina,
PrasRaves Mia L.,
Ferdinandusse Sacha,
Vervaart Martin A. T.,
Luyf Angela C. M.,
Kampen Antoine H. C.,
Wanders Ronald J. A.,
Waterham Hans R.,
Vaz Frédéric M.
Publication year - 2018
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-017-0076-9
Subject(s) - peroxisome , lipidome , biochemistry , lipidomics , peroxisomal disorder , zellweger syndrome , phospholipid , enzyme , chemistry , plasmalogen , oxidase test , biology , membrane , gene
Peroxisomes play an important role in a variety of metabolic pathways, including the α‐ and β‐oxidation of fatty acids, and the biosynthesis of ether phospholipids. Single peroxisomal enzyme deficiencies (PEDs) are a group of peroxisomal disorders in which either a peroxisomal matrix enzyme or a peroxisomal membrane transporter protein is deficient. To investigate the functional consequences of specific enzyme deficiencies on the lipidome, we performed lipidomics using cultured skin fibroblasts with different defects in the β‐oxidation of very long‐chain fatty acids, including ABCD1‐ (ALD), acyl‐CoA oxidase 1 (ACOX1)‐, D‐bifunctional protein (DBP)‐, and acyl‐CoA binding domain containing protein 5 (ACBD5)‐deficient cell lines. Ultra‐high performance liquid chromatography coupled with high‐resolution mass spectrometry revealed characteristic changes in the phospholipid composition in fibroblasts with different fatty acid β‐oxidation defects. Remarkably, we found that ether phospholipids, including plasmalogens, were decreased. We defined specific phospholipid ratios reflecting the different enzyme defects, which can be used to discriminate the PED fibroblasts from healthy control cells.