The important role of the central intermediary metabolite acetyl-coenzyme A (AcCoA)for several anabolic and catabolic pathways is well characterised. However, the role of AcCoA as the only known donor of acetyl groups for protein acetylation in regulation of enzyme activities, protein complex stability as well as epigenetic status off chromatin, is only recently emerging. Among multiple other pathways, the autophagy pathway has now been shown to be directly regulated by protein acetylation and deacetylation. Therefore, it was reasoned that the availability of AcCoA, via the modulation of AcCoA generating enzymes, may regulate autophagy. This study has focussed on the role of the acetate-mediated route to nuclear-cytosolic AcCoA synthesis, catalysed by AcCoA synthetase 2 (ACSS2), in the regulation of autophagy.