Weikang Ma, Chahida Chaami, Elise Gerlach Melhedegaard, Christopher T A Lewis, Chengxin Zhang, Meihua Guo, Hailey Flannagan, Maicon Landim-Vieira, W Glen Pyle, Kenneth S Campbell, Julien Ochala
Systolic heart failure is increasingly recognized as a disease of impaired cardiac energy metabolism. Here, the authors show that cardiac myosin super-relaxation (an energy-conserving myosin state) is destabilized in failing human myocardium. Importantly, this loss of energy conservation is associated with elevated post-translational modifications (phosphorylation and acetylation) rather than gross structural changes in thick filament organization. Hence, targeting post-translational modifications signaling pathways opens new therapeutic opportunities.