Metabolic switch from fatty acid oxidation to glycolysis in knock-in mouse model of Barth syndrome
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00576227" target="_blank" >RIV/68378050:_____/23:00576227 - isvavai.cz</a>
Result on the web
<a href="https://www.embopress.org/doi/full/10.15252/emmm.202317399" target="_blank" >https://www.embopress.org/doi/full/10.15252/emmm.202317399</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15252/emmm.202317399" target="_blank" >10.15252/emmm.202317399</a>
Alternative languages
Result language
angličtina
Original language name
Metabolic switch from fatty acid oxidation to glycolysis in knock-in mouse model of Barth syndrome
Original language description
Mitochondria are central for cellular metabolism and energy supply. Barth syndrome (BTHS) is a severe disorder, due to dysfunction of the mitochondrial cardiolipin acyl transferase tafazzin. Altered cardiolipin remodeling affects mitochondrial inner membrane organization and function of membrane proteins such as transporters and the oxidative phosphorylation (OXPHOS) system. Here, we describe a mouse model that carries a G197V exchange in tafazzin, corresponding to BTHS patients. TAZ(G197V) mice recapitulate disease-specific pathology including cardiac dysfunction and reduced oxidative phosphorylation. We show that mutant mitochondria display defective fatty acid-driven oxidative phosphorylation due to reduced levels of carnitine palmitoyl transferases. A metabolic switch in ATP production from OXPHOS to glycolysis is apparent in mouse heart and patient iPSC cell-derived cardiomyocytes. An increase in glycolytic ATP production inactivates AMPK causing altered metabolic signaling in TAZ(G197V). Treatment of mutant cells with AMPK activator reestablishes fatty acid-driven OXPHOS and protects mice against cardiac dysfunction.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EMBO Molecular Medicine
ISSN
1757-4676
e-ISSN
1757-4684
Volume of the periodical
15
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
21
Pages from-to
e17399
UT code for WoS article
001041495700001
EID of the result in the Scopus database
2-s2.0-85166675912