Alessandro Matte, Anand Babu Wilson, Federica Gevi, Enrica Federti, Antonio Recchiuti, Giulia Ferri, Anna Maria Brunati, Mario Angelo Pagano, Roberta Russo, Christophe Leboeuf, Anne Janin, Anna Maria Timperio, Achille Iolascon, Elisa Gremese, Lenny Dang, Narla Mohandas, Carlo Brugnara, Lucia De Franceschi
Hereditary spherocytosis (HS) is the most common non-immune hereditary chronic hemolytic anemia after hemoglobinopathies. The genetic defects in membrane function causing HS leads to perturbation of red cell metabolome, with altered glycolysis. In mice genetically lacking protein 4.2 (4.2-/-, Epb42), a murine model of HS, we show increased expression of pyruvate kinase (Pk) isoforms in whole and fractioned red cells in conjunction with abnormalities in the glycolytic pathway and in GSH system. Mitapivat, a PKs activator, metabolically re-programs 4...
September 7, 2023: JCI Insight