Deacetylation by SIRT3 Relieves Inhibition of Mitochondrial Protein Function

Lysine acetylation is a chemical modification occurring on cellular proteins that plays important roles in protein regulation. In mitochondria, protein acetylation is regulated by the sirtuin SIRT3, which has been reported to control several metabolic pathways. While the functional relevance of protein acetylation is likely specific for proteins in different pathways, a picture is emerging for mitochondrial protein acetylation to be an important regulator of enzymatic activity. In this review, we integrate qualitative and quantitative proteomic acetylation studies and put forward the hypothesis that acetylation suppresses enzymatic activity, and that SIRT3 serves to relieve the suppression. We discuss the possible mechanisms of suppression, and the future studies needed to fully understand the biological role of acetylation and its regulation by the sirtuins.