Project B05 (Szendrödi/Westenfeld)
Mitochondrial efficacy in AMI: role of PGC-1α
In skeletal muscle of mice, the splicing isoform of PPAR-gamma-coactivator-1-alpha (PGC-1α) one is a main regulator of mitochondrial function, while the isoform PGC-1α four mediates exercise-induced hypertrophy. Humans with T2DM display reduced whole-PGC1α expression. In cardiomyocyte-specific PGC1α4 knockout mice, we observed impaired contractile function after AMI. We hypothesize PGC1α as a master switch of remote myocardial function: PGC1α1 increases efficient mitochondrial energy generation, PGC1α4 preserves contractile function. We will identify myocardial adaptation through regulation of PGC1α-isoforms and impact of T2DM on this signaling cascade.