Our observations are consistent with some studies suggesting that NRF1/2 activation prevents diabetic cardiomyopathy,35 whereas they refute others who have reported ERR downregulation as a key mechanism in decreased expression of PGC-1 target genes in heart failure.29 We surmise that future studies identifying the mechanism of selective dysregulation of NRF2-dependent antioxidant gene expression will provide clues to therapies for the restoration of mitochondrial function in chagasic hearts. This evidence concerns the gene NRF1 and diabetic cardiomyopathy.