Blocking phosphatidylglycerol degradation in yeast defective in cardiolipin remodeling results in a new model of the Barth syndrome cellular phenotype

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

Blocking phosphatidylglycerol degradation in yeast defective in cardiolipin remodeling results in a new model of the Barth syndrome cellular phenotype

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/GA19-04052S" target="_blank" >GA19-04052S: Function of specific membrane microdomains in lipid homeostasis</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Volume of the periodical

298

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

101462

UT code for WoS article

000748357700012

EID of the result in the Scopus database

2-s2.0-85122067524