Accumulation of cardiolipin and lysocardiolipin in fibroblasts from Tangier disease subjects

• Published in: FEBS letters Vol. 500; no. 3; pp. 157 - 162
• Main Authors: Fobker, Manfred, Voss, Reinhard, Reinecke, Holger, Crone, Christina, Assmann, Gerd, Walter, Michael
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 06.07.2001
• Subjects: ABCA1, ATP binding cassette transporter 1; Adult; Aged; apo A-I, apolipoprotein A-I; Apolipoprotein A-I; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; Biological Transport; Cardiolipin; Cardiolipins - analysis; Cardiolipins - metabolism; Cells, Cultured; Cholesterol - metabolism; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; CL, cardiolipin; DMEM, Dulbecco's modified Eagle's medium; Familial high density lipoprotein deficiency; Female; Fibroblasts - chemistry; Fibroblasts - metabolism; Fibroblasts - pathology; High density lipoprotein; Homozygote; HPLC, high performance liquid chromatography; Humans; LC, lysocardiolipin; Lysocardiolipin; Male; Middle Aged; Niemann–Pick type C disease; NPC disease, Niemann–Pick type C disease; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; Phospholipids - analysis; Phospholipids - metabolism; PI, phosphatidylinositol; PLD, phospholipase D; Sensitivity and Specificity; SM, sphingomyelin; Spectrometry, Mass, Secondary Ion; Sterol trafficking; Tangier disease; Tangier Disease - genetics; Tangier Disease - metabolism; Tangier Disease - pathology; TD, Tangier disease; TLC, thin layer chromatography; TOF SIMS, time-of-flight secondary ion mass spectrometry; NPC disease, Niemann–Pick type C disease; LC, lysocardiolipin; TLC, thin layer chromatography; High density lipoprotein; SM, sphingomyelin; Sterol trafficking; HPLC, high performance liquid chromatography; Lysocardiolipin; ABCA1, ATP binding cassette transporter 1; PI, phosphatidylinositol; PA, phosphatidic acid; PC, phosphatidylcholine; TD, Tangier disease; TOF SIMS, time-of-flight secondary ion mass spectrometry; apo A-I, apolipoprotein A-I; Familial high density lipoprotein deficiency; CL, cardiolipin; PE, phosphatidylethanolamine; ATP binding cassette transporter 1; DMEM, Dulbecco’s modified Eagle’s medium; Apolipoprotein A-I; PLD, phospholipase D; Tangier disease; Cardiolipin; Niemann–Pick type C disease
• DOI: 10.1016/S0014-5793(01)02578-9
• ISSN: 0014-5793

Tangier disease (TD) is an inherited disorder of lipid metabolism characterized by very low high density lipoprotein (HDL) plasma levels, cellular cholesteryl ester accumulation and reduced cholesterol excretion in response to HDL apolipoproteins. Molecular defects in the ATP binding cassette transporter 1 (ABCA1) have recently been identified as the cause of TD. ABCA1 plays a key role in the translocation of cholesterol across the plasma membrane, and defective ABCA1 causes cholesterol storage in TD cells. Not only cholesterol efflux, but also phospholipid efflux was shown to be impaired in TD cells. By use of thin layer chromatography, high performance liquid chromatography and time-of-flight secondary ion mass spectrometry, we characterized the cellular phospholipid content in fibroblasts from three homozygous TD patients. The cellular content of the major phospholipids was not found to be significantly altered in TD fibroblasts. However, the two phospholipids cardiolipin and lysocardiolipin, which make up minute amounts in normal cells, were at least 3–5-fold enriched in fibroblasts from TD subjects. A structurally closely related phospholipid (lysobisphosphatidic acid) has recently been shown to be enriched in Niemann–Pick type C, another lipid storage disorder. Altogether these data may indicate that the role of these phospholipids is a regulatory one rather than that of a bulk mediator of cholesterol solubilization in sterol trafficking and efflux.