Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residue are novel post-translational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day old rabbit hearts. Cardiac fatty acid β-oxidation rates increased in 21-day vs. 1- and 7-day old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day old hearts. The fatty acid oxidation enzymes, long chain acyl CoA dehydrogenase (LCAD) and β-hydroxyacyl CoA dehydrogenase (β-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid β-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, GCN5L1, as silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and β-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of PGC-1α, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxia-inducible factor-1α, hexokinase, and phosphoglycerate mutase expression declined post-birth, whereas acetylation of these glycolytic enzymes increased. Pyruvate dehydrogenase (PDH), its phosphorylation rather than acetylation increased in 21-day old hearts, accounting for the low glucose oxidation post birth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data is the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation.
- newborn heart
- energy metabolism
- myocardial fatty acid oxidation
- lysine acetylation
- lysine succinylation
- Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology