Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation

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Barth syndrome : cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. / Gonzalvez, François; D'Aurelio, Marilena; Boutant, Marie; Moustapha, Aoula; Puech, Jean-Philippe; Landes, Thomas; Arnauné-Pelloquin, Laeticia; Vial, Guillaume; Taleux, Nellie; Slomianny, Christian; Wanders, Ronald J; Houtkooper, Riekelt H; Bellenguer, Pascale; Møller, Ian Max; Gottlieb, Eyal; Vaz, Frederic M; Manfredi, Giovanni; Petit, Patrice X.

I: B B A - Molecular Basis of Disease, Bind 1832, Nr. 8, 08.2013, s. 1194-1206.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Gonzalvez, F, D'Aurelio, M, Boutant, M, Moustapha, A, Puech, J-P, Landes, T, Arnauné-Pelloquin, L, Vial, G, Taleux, N, Slomianny, C, Wanders, RJ, Houtkooper, RH, Bellenguer, P, Møller, IM, Gottlieb, E, Vaz, FM, Manfredi, G & Petit, PX 2013, 'Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation', B B A - Molecular Basis of Disease, bind 1832, nr. 8, s. 1194-1206. https://doi.org/10.1016/j.bbadis.2013.03.005

APA

Gonzalvez, F., D'Aurelio, M., Boutant, M., Moustapha, A., Puech, J-P., Landes, T., Arnauné-Pelloquin, L., Vial, G., Taleux, N., Slomianny, C., Wanders, R. J., Houtkooper, R. H., Bellenguer, P., Møller, I. M., Gottlieb, E., Vaz, F. M., Manfredi, G., & Petit, P. X. (2013). Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. B B A - Molecular Basis of Disease, 1832(8), 1194-1206. https://doi.org/10.1016/j.bbadis.2013.03.005

CBE

Gonzalvez F, D'Aurelio M, Boutant M, Moustapha A, Puech J-P, Landes T, Arnauné-Pelloquin L, Vial G, Taleux N, Slomianny C, Wanders RJ, Houtkooper RH, Bellenguer P, Møller IM, Gottlieb E, Vaz FM, Manfredi G, Petit PX. 2013. Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. B B A - Molecular Basis of Disease. 1832(8):1194-1206. https://doi.org/10.1016/j.bbadis.2013.03.005

MLA

Vancouver

Author

Gonzalvez, François ; D'Aurelio, Marilena ; Boutant, Marie ; Moustapha, Aoula ; Puech, Jean-Philippe ; Landes, Thomas ; Arnauné-Pelloquin, Laeticia ; Vial, Guillaume ; Taleux, Nellie ; Slomianny, Christian ; Wanders, Ronald J ; Houtkooper, Riekelt H ; Bellenguer, Pascale ; Møller, Ian Max ; Gottlieb, Eyal ; Vaz, Frederic M ; Manfredi, Giovanni ; Petit, Patrice X. / Barth syndrome : cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. I: B B A - Molecular Basis of Disease. 2013 ; Bind 1832, Nr. 8. s. 1194-1206.

Bibtex

@article{45d629ec739f46bbafcab31d5405847c,
title = "Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation",
abstract = "Cardiolipin is a mitochondrion-specific phospholipid that stabilizes the assembly of respiratory chain complexes, favoring full-yield operation. It also mediates key steps in apoptosis. In Barth syndrome, an X chromosome-linked cardiomyopathy caused by tafazzin mutations, cardiolipins display acyl chain modifications and are present at abnormally low concentrations, whereas monolysocardiolipin accumulates. Using immortalized lymphoblasts from Barth syndrome patients, we showed that the production of abnormal cardiolipin led to mitochondrial alterations. Indeed, the lack of normal cardiolipin led to changes in electron transport chain stability, resulting in cellular defects. We found a destabilization of the supercomplex (respirasome) I+III2+IVn but also decreased amounts of individual complexes I and IV and supercomplexes I+III and III+IV. No changes were observed in the amounts of individual complex III and complex II. We also found decreased levels of complex V. This complex is not part of the supercomplex suggesting that cardiolipin is required not only for the association/stabilization of the complexes into supercomplexes but also for the modulation of the amount of individual respiratory chain complexes. However, these alterations were compensated by an increase in mitochondrial mass, as demonstrated by electron microscopy and measurements of citrate synthase activity. We suggest that this compensatory increase in mitochondrial content prevents a decrease in mitochondrial respiration and ATP synthesis in the cells. We also show, by extensive flow cytometry analysis, that the type II apoptosis pathway was blocked at the mitochondrial level and that the mitochondria of patients with Barth syndrome cannot bind active caspase-8. Signal transduction is thus blocked before any mitochondrial event can occur. Remarkably, basal levels of superoxide anion production were slightly higher in patients' cells than in control cells as previously evidenced via an increased protein carbonylation in the taz1Δ mutant in the yeast. This may be deleterious to cells in the long term. The consequences of mitochondrial dysfunction and alterations to apoptosis signal transduction are considered in light of the potential for the development of future treatments.",
keywords = "Adenosine Triphosphate, Apoptosis, Barth Syndrome, Cardiolipins, Caspase 8, Cell Death, Cell Line, Citrate (si)-Synthase, Electron Transport Chain Complex Proteins, Humans, Lymphocytes, Lysophospholipids, Mitochondria, Mutation, Signal Transduction, Superoxides, Transcription Factors",
author = "Fran{\c c}ois Gonzalvez and Marilena D'Aurelio and Marie Boutant and Aoula Moustapha and Jean-Philippe Puech and Thomas Landes and Laeticia Arnaun{\'e}-Pelloquin and Guillaume Vial and Nellie Taleux and Christian Slomianny and Wanders, {Ronald J} and Houtkooper, {Riekelt H} and Pascale Bellenguer and M{\o}ller, {Ian Max} and Eyal Gottlieb and Vaz, {Frederic M} and Giovanni Manfredi and Petit, {Patrice X}",
note = "Copyright {\textcopyright} 2013 Elsevier B.V. All rights reserved.",
year = "2013",
month = aug,
doi = "10.1016/j.bbadis.2013.03.005",
language = "English",
volume = "1832",
pages = "1194--1206",
journal = "B B A - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier BV",
number = "8",

}

RIS

TY - JOUR

T1 - Barth syndrome

T2 - cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation

AU - Gonzalvez, François

AU - D'Aurelio, Marilena

AU - Boutant, Marie

AU - Moustapha, Aoula

AU - Puech, Jean-Philippe

AU - Landes, Thomas

AU - Arnauné-Pelloquin, Laeticia

AU - Vial, Guillaume

AU - Taleux, Nellie

AU - Slomianny, Christian

AU - Wanders, Ronald J

AU - Houtkooper, Riekelt H

AU - Bellenguer, Pascale

AU - Møller, Ian Max

AU - Gottlieb, Eyal

AU - Vaz, Frederic M

AU - Manfredi, Giovanni

AU - Petit, Patrice X

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/8

Y1 - 2013/8

N2 - Cardiolipin is a mitochondrion-specific phospholipid that stabilizes the assembly of respiratory chain complexes, favoring full-yield operation. It also mediates key steps in apoptosis. In Barth syndrome, an X chromosome-linked cardiomyopathy caused by tafazzin mutations, cardiolipins display acyl chain modifications and are present at abnormally low concentrations, whereas monolysocardiolipin accumulates. Using immortalized lymphoblasts from Barth syndrome patients, we showed that the production of abnormal cardiolipin led to mitochondrial alterations. Indeed, the lack of normal cardiolipin led to changes in electron transport chain stability, resulting in cellular defects. We found a destabilization of the supercomplex (respirasome) I+III2+IVn but also decreased amounts of individual complexes I and IV and supercomplexes I+III and III+IV. No changes were observed in the amounts of individual complex III and complex II. We also found decreased levels of complex V. This complex is not part of the supercomplex suggesting that cardiolipin is required not only for the association/stabilization of the complexes into supercomplexes but also for the modulation of the amount of individual respiratory chain complexes. However, these alterations were compensated by an increase in mitochondrial mass, as demonstrated by electron microscopy and measurements of citrate synthase activity. We suggest that this compensatory increase in mitochondrial content prevents a decrease in mitochondrial respiration and ATP synthesis in the cells. We also show, by extensive flow cytometry analysis, that the type II apoptosis pathway was blocked at the mitochondrial level and that the mitochondria of patients with Barth syndrome cannot bind active caspase-8. Signal transduction is thus blocked before any mitochondrial event can occur. Remarkably, basal levels of superoxide anion production were slightly higher in patients' cells than in control cells as previously evidenced via an increased protein carbonylation in the taz1Δ mutant in the yeast. This may be deleterious to cells in the long term. The consequences of mitochondrial dysfunction and alterations to apoptosis signal transduction are considered in light of the potential for the development of future treatments.

AB - Cardiolipin is a mitochondrion-specific phospholipid that stabilizes the assembly of respiratory chain complexes, favoring full-yield operation. It also mediates key steps in apoptosis. In Barth syndrome, an X chromosome-linked cardiomyopathy caused by tafazzin mutations, cardiolipins display acyl chain modifications and are present at abnormally low concentrations, whereas monolysocardiolipin accumulates. Using immortalized lymphoblasts from Barth syndrome patients, we showed that the production of abnormal cardiolipin led to mitochondrial alterations. Indeed, the lack of normal cardiolipin led to changes in electron transport chain stability, resulting in cellular defects. We found a destabilization of the supercomplex (respirasome) I+III2+IVn but also decreased amounts of individual complexes I and IV and supercomplexes I+III and III+IV. No changes were observed in the amounts of individual complex III and complex II. We also found decreased levels of complex V. This complex is not part of the supercomplex suggesting that cardiolipin is required not only for the association/stabilization of the complexes into supercomplexes but also for the modulation of the amount of individual respiratory chain complexes. However, these alterations were compensated by an increase in mitochondrial mass, as demonstrated by electron microscopy and measurements of citrate synthase activity. We suggest that this compensatory increase in mitochondrial content prevents a decrease in mitochondrial respiration and ATP synthesis in the cells. We also show, by extensive flow cytometry analysis, that the type II apoptosis pathway was blocked at the mitochondrial level and that the mitochondria of patients with Barth syndrome cannot bind active caspase-8. Signal transduction is thus blocked before any mitochondrial event can occur. Remarkably, basal levels of superoxide anion production were slightly higher in patients' cells than in control cells as previously evidenced via an increased protein carbonylation in the taz1Δ mutant in the yeast. This may be deleterious to cells in the long term. The consequences of mitochondrial dysfunction and alterations to apoptosis signal transduction are considered in light of the potential for the development of future treatments.

KW - Adenosine Triphosphate

KW - Apoptosis

KW - Barth Syndrome

KW - Cardiolipins

KW - Caspase 8

KW - Cell Death

KW - Cell Line

KW - Citrate (si)-Synthase

KW - Electron Transport Chain Complex Proteins

KW - Humans

KW - Lymphocytes

KW - Lysophospholipids

KW - Mitochondria

KW - Mutation

KW - Signal Transduction

KW - Superoxides

KW - Transcription Factors

U2 - 10.1016/j.bbadis.2013.03.005

DO - 10.1016/j.bbadis.2013.03.005

M3 - Journal article

C2 - 23523468

VL - 1832

SP - 1194

EP - 1206

JO - B B A - Molecular Basis of Disease

JF - B B A - Molecular Basis of Disease

SN - 0925-4439

IS - 8

ER -