Gonnot 2023 Nat Commun

Gonnot F, Boulogne L, Brun C, Dia M, Gouriou Y, Bidaux G, Chouabe C, Crola Da Silva C, Ducreux S, Pillot B, Kaczmarczyk A, Leon C, Chanon S, Perret C, Sciandra F, Dargar T, Gache V, Farhat F, Sebbag L, Bochaton T, Thibault H, Ovize M, Paillard M, Gomez L (2023) SERCA2 phosphorylation at serine 663 is a key regulator of Ca²⁺ homeostasis in heart diseases. https://doi.org/10.1038/s41467-023-39027-x

» Nat Commun 14:3346. PMID: 37291092 Open Access

Gonnot Fabrice, Boulogne Laura, Brun Camille, Dia Maya, Gouriou Yves, Bidaux Gabriel, Chouabe Christophe, Crola Da Silva Claire, Ducreux Sylvie, Pillot Bruno, Kaczmarczyk Andrea, Leon Christelle, Chanon Stephanie, Perret Coralie, Sciandra Franck, Dargar Tanushri, Gache Vincent, Farhat Fadi, Sebbag Laurent, Bochaton Thomas, Thibault Helene, Ovize Michel, Paillard Melanie, Gomez Ludovic (2023) Nat Commun

Abstract: Despite advances in cardioprotection, new therapeutic strategies capable of preventing ischemia-reperfusion injury of patients are still needed. Here, we discover that sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA2) phosphorylation at serine 663 is a clinical and pathophysiological event of cardiac function. Indeed, the phosphorylation level of SERCA2 at serine 663 is increased in ischemic hearts of patients and mouse. Analyses on different human cell lines indicate that preventing serine 663 phosphorylation significantly increases SERCA2 activity and protects against cell death, by counteracting cytosolic and mitochondrial Ca²⁺ overload. By identifying the phosphorylation level of SERCA2 at serine 663 as an essential regulator of SERCA2 activity, Ca²⁺ homeostasis and infarct size, these data contribute to a more comprehensive understanding of the excitation/contraction coupling of cardiomyocytes and establish the pathophysiological role and the therapeutic potential of SERCA2 modulation in acute myocardial infarction, based on the hotspot phosphorylation level of SERCA2 at serine 663 residue.

• Bioblast editor: Plangger M • O2k-Network Lab: FR Lyon Ovize M

Labels: MiParea: Respiration Pathology: Cardiovascular Stress:Ischemia-reperfusion Organism: Mouse Tissue;cell: Heart Preparation: Intact cells

Regulation: Calcium Coupling state: LEAK, ROUTINE, ET Pathway: ROX HRR: Oxygraph-2k

2023-06