Regulation of intermediary metabolism by protein acetylation

KL Guan, Y Xiong - Trends in biochemical sciences, 2011 - cell.com
Trends in biochemical sciences, 2011cell.com
Extensive studies during the past four decades have identified important roles for lysine
acetylation in the regulation of nuclear transcription. Recent proteomic analyses on protein
acetylation uncovered a large number of acetylated proteins in the cytoplasm and
mitochondria, including most enzymes involved in intermediate metabolism. Acetylation
regulates metabolic enzymes by multiple mechanisms, including via enzymatic activation or
inhibition, and by influencing protein stability. Conversely, non-nuclear NAD+-dependent …
Extensive studies during the past four decades have identified important roles for lysine acetylation in the regulation of nuclear transcription. Recent proteomic analyses on protein acetylation uncovered a large number of acetylated proteins in the cytoplasm and mitochondria, including most enzymes involved in intermediate metabolism. Acetylation regulates metabolic enzymes by multiple mechanisms, including via enzymatic activation or inhibition, and by influencing protein stability. Conversely, non-nuclear NAD+-dependent sirtuin deacetylases can regulate cellular and organismal metabolism, possibly through direct deacetylation of metabolic enzymes. Furthermore, acetylation of metabolic enzymes is highly conserved from prokaryotes to eukaryotes. Given the frequent occurrence of metabolic dysregulation in diabetes, obesity and cancer, enzymes modulating acetylation could provide attractive targets for therapeutic intervention for these diseases.
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