In recent years, reversible acetylation, which is a post-translational modification (PTM) in which an acetyl group is added to a lysine residue, has been proposed to link metabolic flux to cellular signaling and the adaptive response. This is due to the fact that two fundamental metabolites central to cellular/energy metabolism, NAD+ and acetyl CoA, are key substrates for the sirtuin (SIRT) deacetylases (DACs) and acetyltransferases (ACTs), respectively. DACs remove acetyl groups from lysine residues, whilst ACTs add them. Given that exercise results in fluctuations in acetyl CoA and NAD+, reversible acetylation presents as an interesting molecular signalling mechanism for regulating protein activity and transcriptional control, which are important control points for mitochondrial biogenesis. This talk will cover recent studies looking at the role of ACTs and DACs in regulating mitochondrial biogenesis, with particular focus on the role of the ACTs, p300 and general control of amino acid synthesis 5 (GCN5).