Nicotinamide Mononucleotide Alleviates Cardiomyopathy Phenotypes Caused by Short-Chain Enoyl-Coa Hydratase 1 Deficiency

•ECHS1 hydrates medium- and short-chain enoyl CoAs and catalyzes the oxidation of fatty acids and branched-chain amino acids.•The mechanism driving ECHS1 deficiency–associated cardiomyopathy was investigated using conventional biochemistry and molecular biology methods, including immunoprecipitation and polymerase chain reaction.•Echs1 heterogeneous knockout mice displayed cardiac dysfunction as evaluated by echocardiography.•ECHS1 deficiency causes cardiomyopathy by enhancing p300-mediated H3K9ac.•ECHS1 deficiency–induced cardiomyopathy can be prevented using an intervention approach targeting H3K9ac.