Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis

Fredoen Valianpour, Voula Mitsakos, Dimitri Schlemmer, Jeffrey Towbin, Juliet M. Taylor, Paul G. Ekert, David R. Thorburn, Arnold Munnich, Ronald J.A. Wanders, Peter G. Barth, Frédéric M. Vaz

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1182-1195
Number of pages14
JournalJournal of Lipid Research
Volume46
Issue number6
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

Fingerprint

Barth Syndrome
Apoptosis
Cardiolipins
Yeast
BH3 Interacting Domain Death Agonist Protein
Fatty Acids
Apoptosomes
Lysophospholipids
Death Domain Receptors
Lymphocytes
Mitochondrial Membranes
Cell death
Fibroblasts
Platelets
Cytochromes c
monolysocardiolipin
Chemical analysis
Saccharomyces cerevisiae
Muscle
Phospholipids

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Valianpour, F., Mitsakos, V., Schlemmer, D., Towbin, J., Taylor, J. M., Ekert, P. G., ... Vaz, F. M. (2005). Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis. Journal of Lipid Research, 46(6), 1182-1195. https://doi.org/10.1194/jlr.M500056-JLR200

Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis. / Valianpour, Fredoen; Mitsakos, Voula; Schlemmer, Dimitri; Towbin, Jeffrey; Taylor, Juliet M.; Ekert, Paul G.; Thorburn, David R.; Munnich, Arnold; Wanders, Ronald J.A.; Barth, Peter G.; Vaz, Frédéric M.

In: Journal of Lipid Research, Vol. 46, No. 6, 01.12.2005, p. 1182-1195.

Research output: Contribution to journalArticle

Valianpour, F, Mitsakos, V, Schlemmer, D, Towbin, J, Taylor, JM, Ekert, PG, Thorburn, DR, Munnich, A, Wanders, RJA, Barth, PG & Vaz, FM 2005, 'Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis', Journal of Lipid Research, vol. 46, no. 6, pp. 1182-1195. https://doi.org/10.1194/jlr.M500056-JLR200
Valianpour, Fredoen ; Mitsakos, Voula ; Schlemmer, Dimitri ; Towbin, Jeffrey ; Taylor, Juliet M. ; Ekert, Paul G. ; Thorburn, David R. ; Munnich, Arnold ; Wanders, Ronald J.A. ; Barth, Peter G. ; Vaz, Frédéric M. / Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis. In: Journal of Lipid Research. 2005 ; Vol. 46, No. 6. pp. 1182-1195.
@article{d22e9a255cff4e058361fe839223e0e6,
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.",
author = "Fredoen Valianpour and Voula Mitsakos and Dimitri Schlemmer and Jeffrey Towbin and Taylor, {Juliet M.} and Ekert, {Paul G.} and Thorburn, {David R.} and Arnold Munnich and Wanders, {Ronald J.A.} and Barth, {Peter G.} and Vaz, {Fr{\'e}d{\'e}ric M.}",
year = "2005",
month = "12",
day = "1",
doi = "10.1194/jlr.M500056-JLR200",
language = "English (US)",
volume = "46",
pages = "1182--1195",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "6",

}

TY - JOUR

T1 - Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis

AU - Valianpour, Fredoen

AU - Mitsakos, Voula

AU - Schlemmer, Dimitri

AU - Towbin, Jeffrey

AU - Taylor, Juliet M.

AU - Ekert, Paul G.

AU - Thorburn, David R.

AU - Munnich, Arnold

AU - Wanders, Ronald J.A.

AU - Barth, Peter G.

AU - Vaz, Frédéric M.

PY - 2005/12/1

Y1 - 2005/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=24944563130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24944563130&partnerID=8YFLogxK

U2 - 10.1194/jlr.M500056-JLR200

DO - 10.1194/jlr.M500056-JLR200

M3 - Article

VL - 46

SP - 1182

EP - 1195

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 6

ER -