Dietary influence on protein post-translational modifications: insights on protein acetylation and malonylation

Post-translational modification (PTM) of amino acid residues regulates protein function, activity, structure, and localization. Acetylation and malonylation are two major acylated modifications occurring in various proteins, especially on the ε-amine group in lysine residues. It has long been known that these lysine acylations are modulated by SIRT enzymes; however, they can also be regulated non-enzymatically. Both acetylation and malonylation PTM have been identified in histone and non-histone proteins. Since both acetyl-CoA and malonyl-CoA, substrates for acetylation and malonylation respectively, are by-products of the Krebs cycle, lysine acetylation and malonylation are commonly found in proteins involved in metabolic processes. Diet composition is known to regulate many catabolic and anabolic metabolic processes such as glycolysis, fatty acid oxidation, lipogenesis, and oxidative phosphorylation. In our study, we used C57BL/6 female mice and fed them three different diets from 8 weeks of age for 8 weeks: normal chow diet (74% carb (67% from starch), 20% protein, and 6% fat), high sugar diet ( 74% Carb (57% from sucrose), 20% protein, and 6% fat), and ketogenic diet (1% carb, 9% protein, and 90% fat). Immunoaffinity purification followed by label-free detection of acetylated and malonylated lysine peptides in the mice livers on the three different diets and compared the fold changes of these peptides across the diets. This study provides invaluable information on how diets can modify different acylation PTMs and offers insights into microscopic changes in proteins related to these diets, with implications for various diseases and diet therapies.