Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells
Cardiolipin (CL) optimizes diverse mitochondrial processes, including oxidative phosphorylation (OXPHOS). To function properly, CL needs to be unsaturated, which requires the acyltransferase Tafazzin (TAZ). Loss-of-function mutations in the TAZ gene are responsible for the Barth syndrome (BTHS), a r...
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doaj-767f43c175a146e093a1de1bb02bb5712020-11-25T00:30:26ZengShared Science Publishers OGMicrobial Cell2311-26382018-02-015522023210.15698/mic2018.05.629Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cellsMaxence de Taffin de Tilques0Jean-Paul Lasserre1François Godard2Elodie Sardin3Marine Bouhier4Marina Le Guedard5Roza Kucharczyk6Patrice X. Petit7Eric Testet8Jean-Paul di Rago9Déborah Tribouillard-Tanvier10Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.Laboratoire de Biogenèse Membranaire, CNRS UMR 5200, Université de Bordeaux, INRA Bordeaux Aquitaine, Villenave d’Ornon, France.Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.CNRS FR3636 Fédération de recherché en Neuroscience, Université Paris-Descartes, 45, rue des Saints-Pères, 75006 Paris, France.Laboratoire de Biogenèse Membranaire, CNRS UMR 5200, Université de Bordeaux, INRA Bordeaux Aquitaine, Villenave d’Ornon, France.Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.Cardiolipin (CL) optimizes diverse mitochondrial processes, including oxidative phosphorylation (OXPHOS). To function properly, CL needs to be unsaturated, which requires the acyltransferase Tafazzin (TAZ). Loss-of-function mutations in the TAZ gene are responsible for the Barth syndrome (BTHS), a rare X-linked cardiomyopathy, presumably because of a diminished OXPHOS capacity. Herein we show that a partial inhibition of cytosolic protein synthesis, either chemically with the use of cycloheximide or by specific genetic mutations, fully restores biogenesis and the activity of the oxidative phosphorylation system in a yeast BTHS model (taz1Δ). Interestingly, the defaults in CL were not suppressed, indicating that they are not primarily responsible for the OXPHOS deficiency in taz1Δ yeast. Low concentrations of cycloheximide in the picomolar range were beneficial to TAZ-deficient HeLa cells, as evidenced by the recovery of a good proliferative capacity. These findings reveal that a diminished capacity of CL remodeling deficient cells to preserve protein homeostasis is likely an important factor contributing to the pathogenesis of BTHS. This in turn, identifies cytosolic translation as a potential therapeutic target for the treatment of this disease.http://microbialcell.com/researcharticles/decreasing-cytosolic-translation-is-beneficial-to-yeast-and-human-tafazzin-deficient-cells/mitochondrial diseaseoxidative phosphorylationBarth syndromecytosolic protein synthesiscycloheximidecardiolipin remodeling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maxence de Taffin de Tilques Jean-Paul Lasserre François Godard Elodie Sardin Marine Bouhier Marina Le Guedard Roza Kucharczyk Patrice X. Petit Eric Testet Jean-Paul di Rago Déborah Tribouillard-Tanvier |
spellingShingle |
Maxence de Taffin de Tilques Jean-Paul Lasserre François Godard Elodie Sardin Marine Bouhier Marina Le Guedard Roza Kucharczyk Patrice X. Petit Eric Testet Jean-Paul di Rago Déborah Tribouillard-Tanvier Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells Microbial Cell mitochondrial disease oxidative phosphorylation Barth syndrome cytosolic protein synthesis cycloheximide cardiolipin remodeling |
author_facet |
Maxence de Taffin de Tilques Jean-Paul Lasserre François Godard Elodie Sardin Marine Bouhier Marina Le Guedard Roza Kucharczyk Patrice X. Petit Eric Testet Jean-Paul di Rago Déborah Tribouillard-Tanvier |
author_sort |
Maxence de Taffin de Tilques |
title |
Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells |
title_short |
Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells |
title_full |
Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells |
title_fullStr |
Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells |
title_full_unstemmed |
Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells |
title_sort |
decreasing cytosolic translation is beneficial to yeast and human tafazzin-deficient cells |
publisher |
Shared Science Publishers OG |
series |
Microbial Cell |
issn |
2311-2638 |
publishDate |
2018-02-01 |
description |
Cardiolipin (CL) optimizes diverse mitochondrial processes, including oxidative phosphorylation (OXPHOS). To function properly, CL needs to be unsaturated, which requires the acyltransferase Tafazzin (TAZ). Loss-of-function mutations in the TAZ gene are responsible for the Barth syndrome (BTHS), a rare X-linked cardiomyopathy, presumably because of a diminished OXPHOS capacity. Herein we show that a partial inhibition of cytosolic protein synthesis, either chemically with the use of cycloheximide or by specific genetic mutations, fully restores biogenesis and the activity of the oxidative phosphorylation system in a yeast BTHS model (taz1Δ). Interestingly, the defaults in CL were not suppressed, indicating that they are not primarily responsible for the OXPHOS deficiency in taz1Δ yeast. Low concentrations of cycloheximide in the picomolar range were beneficial to TAZ-deficient HeLa cells, as evidenced by the recovery of a good proliferative capacity. These findings reveal that a diminished capacity of CL remodeling deficient cells to preserve protein homeostasis is likely an important factor contributing to the pathogenesis of BTHS. This in turn, identifies cytosolic translation as a potential therapeutic target for the treatment of this disease. |
topic |
mitochondrial disease oxidative phosphorylation Barth syndrome cytosolic protein synthesis cycloheximide cardiolipin remodeling |
url |
http://microbialcell.com/researcharticles/decreasing-cytosolic-translation-is-beneficial-to-yeast-and-human-tafazzin-deficient-cells/ |
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