Speaker  Professor Uwe Schlattner, Director of the LBFA, Université Grenoble Alpes

Title AMP-activated protein kinase in energy stress: lessons learned from a cardiomyocyte-specific knock-out and a genetically-encoded ATP/ADP sensor

Host Elisabeth Ehler

 

Abstract AMP-activated protein kinase (AMPK) serves as the primary sensor and regulator of cellular energy homeostasis during times of stress. While its role in many organs is well-established, its significance in the non-pathological heart, a highly energy-demanding organ, is not yet entirely clear. We established a cardiomyocyte-specific, inducible AMPK α1/α2 double knock-down mouse model, that revealed important roles of cardiac AMPK at increased cardiac workload, potentially limiting exercise performance. This effect can be primarily attributed to compromised mitochondrial function and bioenergetics, particularly with more advanced age. Intriguingly, some effects of the cardiac AMPK knock-down are sex-specific. Further, we exploited the naturally evolved energy sensing mechanism of AMPK by engineering a genetically-encoded, FRET-based nanosensor. This sensor visualizes critical, physiologically meaningful changes in ATP/ADP and ATP/AMP ratios within living cells. It offers insights into physiological versus toxic stress conditions based on the early time course of the signal.