Mitochondrial efficacy in AMI: role of PGC-1α (B05)

• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236177352

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.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1116: Master switches in cardiac ischemia
• Applicant Institution: Heinrich-Heine-Universität Düsseldorf
• Project Heads: Professor Dr. Ulrich Flögel, until 12/2018; Professor Dr. Michael Roden, until 12/2018; Professorin Dr. Julia Szendrödi; Privatdozent Dr. Ralf Westenfeld