3 research outputs found
Vyuziti molekularnich a pocitacove rizenych metod pro diagnostiku poruch pohlavnich bunek a embryi.
The aim of this thesis was to use fluorescent in situ hybridization for the diagnosis of disorders in gametes and embryos. In the second part it was used the computer assisted semen analysis for evaluation of sperm motility.Summary and text also in EnglishAvailable from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi
Metabolic switch from fatty acid oxidation to glycolysis in knockâin mouse model of Barth syndrome
Abstract 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. TAZG197V mice recapitulate diseaseâspecific pathology including cardiac dysfunction and reduced oxidative phosphorylation. We show that mutant mitochondria display defective fatty acidâdriven 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 cellâderived cardiomyocytes. An increase in glycolytic ATP production inactivates AMPK causing altered metabolic signaling in TAZG197V. Treatment of mutant cells with AMPK activator reestablishes fatty acidâdriven OXPHOS and protects mice against cardiac dysfunction