Perturbations of PGC1/PPAR signaling, an important pathway regulating mitochondrial biogenesis and maturation, disrupts CM maturation, whereas PGC1/PPAR activation improves the maturation of pluripotent stem cell-derived CMs.5 Similarly, disruption of ERRα and ERRγ, which function as critical transcriptional activators of metabolic genes in adult CM, impairs cardiac maturation and results in heart failure in the developing heart.19 Findings from this study establish neddylation as a crucial mechanism in the regulation of cardiac oxidative metabolism. Here, PPARGC1A is linked to heart failure.