Abstract:Metabolic reprogramming is a hallmark in both cancer and heart failure. Mutations of the isocitrate deyhydrogenase (IDH) 1 and 2 cause metabolic dysfunction in cancer cells through overproduction of the oncometabolite D-2-hydroxyglutarate (D2-HG) and are associated with cardiomyopathy. We recently discovered that alpha-Ketoglutarate dehydrogenase inhibition by D2-HG redirects Krebs cycle flux. This implies a central role for IDH and ATP citrate lyase (ACL) in regulating reductive formation of citrate and histo… Show more
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