Accumulation of cardiolipin and lysocardiolipin in fibroblasts from Tangier disease subjects

Tangier disease (TD) is an inherited disorder of lipid metabolism character ized by very low high density lipoprotein (HDL) plasma levels, cellular cho lesteryl ester accumulation and reduced cholesterol excretion in response t o HDL apolipoproteins, Molecular defects in the ATP binding cassette transp orter 1 (ABCA1) have recently been identified as the cause of TD. ASCA1 pla ys a key role in the translocation of cholesterol across the plasma membran e, and defective ABCA1 causes cholesterol storage in TD cells, Not only cho lesterol efflux, but also phospholipid efflux was shown to be impaired in T D cells. By use of thin layer chromatography, high performance liquid chrom atography and time-of-flight secondary ion mass spectrometry, we characteri zed 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 phospholipi ds cardiolipin and lysocardiolipin, which make up minute amounts in normal cells, were at least 3-5-fold enriched in fibroblasts from TD subjects. A s tructurally closely related phospholipid (lysobisphosphatidic acid) has rec ently been shown to be enriched in Niemann-Pick type C. another lipid stora ge disorder, Altogether these data may indicate that the role of these phos pholipids is a regulatory one rather than that of a bulk mediator of choles terol solubilization in sterol trafficking and efflux. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All r ights reserved.