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Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells

de Taffin de Tilques, Maxence and Lasserre, Jean-Paul and Godard, François and Sardin, Elodie and Bouhier, Marine and Le Guedard, Marina and Kucharczyk, Roza and Petit, Patrice X. and Testet, Eric and di Rago, Jean-Paul and Tribouillard-Tanvier, Déborah (2018) Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells. Microbial Cell, 5 (5). pp. 220-232. ISSN 23112638


Official URL: http://doi.org/10.15698/mic2018.05.629


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.

Item Type:Article
Subjects:Q Science > Q Science (General)
R Medicine > RB Pathology
Divisions:Department of Genetics
ID Code:1553
Deposited By: Dr hab Roza Kucharczyk
Deposited On:19 Oct 2018 08:43
Last Modified:19 Oct 2018 08:43

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