%0 Journal Article
%T SERCA2 phosphorylation at the heart of the disease.
%A Brini M
%A Calì T
%J Cell Calcium
%V 115
%N 0
%D 2023 11 29
%M 37572431
%F 4.69
%R 10.1016/j.ceca.2023.102784
%X Gonnot et al. [1] thoroughly investigated the regulatory role of glycogen synthase kinase 3 beta (GSK3β) in modulating cardiac isoform 2 of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2) activity. They have found that in ischemic hearts of patients and mouse-GSK3β -mediated SERCA2 phosphorylation at serine 663 dampens the SERCA2 pump activity and induces Ca2+ overload which sensitizes towards myocardial ischemia-reperfusion (I/R) injury. The inhibition of serine 663 phosphorylation significantly increases SERCA2 activity and, by preventing cytosolic and mitochondrial Ca2+ overload, reduces cell death during reperfusion. Augmented SERCA2 activity also substantially improves excitation-contraction coupling in cardiomyocytes upon recovery from reperfusion injury. This study provides valuable insights into pathophysiological relevance of GSK3β -mediated SERCA2 phosphorylation in the context of heart diseases and paves the way for designing novel clinical therapeutic approaches to alleviate post infartion heart failure.