We develop a genetic mouse model with myocardial- and mitochondrial-targeted CaMKII overexpression, and find that excessive mitochondrial CaMKII causes dilated cardiomyopathy, without myocardial hypertrophy or death, by reducing expression of assembled complex I and the mitochondrial isoform of creatine kinase (CKmito). This evidence concerns the gene CAMK2G and cardiac hypertrophy.