title: Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis.
abstract: Barth syndrome (BTHS) is an X-linked recessive disorder that is biochemically characterized by low cellular levels of the mitochondrial phospholipid cardiolipin (CL). Previously, we discovered that the yeast disruptant of the TAZ ortholog in Saccharomyces cerevisiae not only displays CL deficiency but also accumulates monolysocardiolipins (MLCLs), which are intermediates in CL remodeling. Therefore, we set out to investigate whether MLCL accumulation also occurs in BTHS. Indeed, we observed MLCL accumulation in heart, muscle, lymphocytes, and cultured lymphoblasts of BTHS patients; however, only very low levels of these lysophospholipids were found in platelets and fibroblasts of these patients. Although the fatty acid composition of the MLCLs was different depending on the tissue source, it did parallel the fatty acid composition of the (remaining) CLs. The possible implications of these findings for the two reported CL remodeling mechanisms, transacylation and deacylation/reacylation, are discussed. Because MLCLs have been proposed to be involved in the initiation of apoptosome-mediated cell death by the sequestration of the proapoptotic protein (t)BH3-interacting domain death agonist (Bid) to the mitochondrial membrane, we used control and BTHS lymphoblasts to investigate whether the accumulation of MLCLs results in higher levels of apoptosis. We found no differences in susceptibility to death receptor-mediated apoptosis or in cellular distribution of Bid, cytochrome c, and other parameters, implying that MLCL accumulation does not lead to enhanced apoptosis in cultured BTHS lymphoblasts.
authors.affiliation: Laboratory of Genetic Metabolic Diseases, Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
authors.forename: Fredoen
authors.initials: F
authors.lastname: Valianpour
authors.forename: Voula
authors.initials: V
authors.lastname: Mitsakos
authors.forename: Dimitri
authors.initials: D
authors.lastname: Schlemmer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Juliet M
authors.initials: JM
authors.lastname: Taylor
authors.forename: Paul G
authors.initials: PG
authors.lastname: Ekert
authors.forename: David R
authors.initials: DR
authors.lastname: Thorburn
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Peter G
authors.initials: PG
authors.lastname: Barth
authors.forename: Frédéric M
authors.initials: FM
authors.lastname: Vaz
mesh_terms: D000215:Acylation; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D009202:Cardiomyopathies / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D016923:Cell Death; D002851:Chromatography, High Pressure Liquid; D041321:Chromosomes, Human, X; D045304:Cytochromes c / Q000378:metabolism; D005808:Genes, Recessive; D008040:Genetic Linkage; D006130:Growth Disorders / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D050356:Lipid Metabolism; D008214:Lymphocytes / Q000378:metabolism; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009135:Muscular Diseases / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013347:Subcellular Fractions; D013577:Syndrome; D019014:fas Receptor / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002308:Cardiolipins; D002352:Carrier Proteins; D008246:Lysophospholipids; D010743:Phospholipids; D019014:fas Receptor; C067188:monolysocardiolipin; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases