Blocking phosphatidylglycerol degradation in yeast defective in cardiolipin remodeling results in a new model of the Barth syndrome cellular phenotype
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F22%3A00567212" target="_blank" >RIV/68378041:_____/22:00567212 - isvavai.cz</a>
Výsledek na webu
<a href="https://linkinghub.elsevier.com/retrieve/pii/S0021925821012710" target="_blank" >https://linkinghub.elsevier.com/retrieve/pii/S0021925821012710</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jbc.2021.101462" target="_blank" >10.1016/j.jbc.2021.101462</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Blocking phosphatidylglycerol degradation in yeast defective in cardiolipin remodeling results in a new model of the Barth syndrome cellular phenotype
Popis výsledku v původním jazyce
Barth syndrome (BTHS) is an inherited mitochondrial disorder characterized by a decrease in total cardiolipin and the accumulation of its precursor monolysocardiolipin due to the loss of the transacylase enzyme tafazzin. However, the molecular basis of BTHS pathology is still not well understood. Here we characterize the double mutant pgc1Ataz1 Delta of Saccharomyces cerevisiae deficient in phosphatidylglycerol-specific phospholipase C and tafazzin as a new yeast model of BTHS. Unlike the taz1 Delta mutant used to date, this model accumulates phosphatidylglycerol, thus better approximating the human BTHS cells. We demonstrate that increased phosphatidylglycerol in this strain leads to more pronounced mitochondrial respiratory defects and an increased incidence of aberrant mitochondria compared to the single taz1 Delta mutant. We also show that the mitochondria of the pgc1 Delta taz1 Delta mutant exhibit a reduced rate of respiration due to decreased cytochrome c oxidase and ATP synthase activities. Finally, we determined that the mood-stabilizing anticonvulsant valproic acid has a positive effect on both lipid composition and mitochondrial function in these yeast BTHS models. Overall, our results show that the pgc1 Delta taz1 Delta mutant better mimics the cellular phenotype of BTHS patients than taz1 Delta cells, both in terms of lipid composition and the degree of disruption of mitochondrial structure and function. This favors the new model for use in future studies.
Název v anglickém jazyce
Blocking phosphatidylglycerol degradation in yeast defective in cardiolipin remodeling results in a new model of the Barth syndrome cellular phenotype
Popis výsledku anglicky
Barth syndrome (BTHS) is an inherited mitochondrial disorder characterized by a decrease in total cardiolipin and the accumulation of its precursor monolysocardiolipin due to the loss of the transacylase enzyme tafazzin. However, the molecular basis of BTHS pathology is still not well understood. Here we characterize the double mutant pgc1Ataz1 Delta of Saccharomyces cerevisiae deficient in phosphatidylglycerol-specific phospholipase C and tafazzin as a new yeast model of BTHS. Unlike the taz1 Delta mutant used to date, this model accumulates phosphatidylglycerol, thus better approximating the human BTHS cells. We demonstrate that increased phosphatidylglycerol in this strain leads to more pronounced mitochondrial respiratory defects and an increased incidence of aberrant mitochondria compared to the single taz1 Delta mutant. We also show that the mitochondria of the pgc1 Delta taz1 Delta mutant exhibit a reduced rate of respiration due to decreased cytochrome c oxidase and ATP synthase activities. Finally, we determined that the mood-stabilizing anticonvulsant valproic acid has a positive effect on both lipid composition and mitochondrial function in these yeast BTHS models. Overall, our results show that the pgc1 Delta taz1 Delta mutant better mimics the cellular phenotype of BTHS patients than taz1 Delta cells, both in terms of lipid composition and the degree of disruption of mitochondrial structure and function. This favors the new model for use in future studies.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10601 - Cell biology
Návaznosti výsledku
Projekt
<a href="/cs/project/GA19-04052S" target="_blank" >GA19-04052S: Funkce specifických membránových mikrodomén v homeostáze lipidů</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Biological Chemistry
ISSN
0021-9258
e-ISSN
1083-351X
Svazek periodika
298
Číslo periodika v rámci svazku
1
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
13
Strana od-do
101462
Kód UT WoS článku
000748357700012
EID výsledku v databázi Scopus
2-s2.0-85122067524