Altered Lysine Acylation of Mitochondrial Proteins in Response to Macronutrient Stresses in the Mouse Liver

摘要

With two-thirds of American adults considered overweight, and a third having metabolic syndrome, nutritional stress contributes to an increasing proportion of disease burden. Identifying the molecular mechanisms leading to metabolic syndrome is therefore critical to improving public health. The mitochondrial sirtuins, SIRT3 and SIRT5, are lysine de-acylases that regulate the activity of mitochondrial proteins and are thought to be an important point of convergence of several metabolic pathways implicated in metabolic syndrome, such as fatty acid oxidation, glycolysis, and amino acid metabolism. We and others have observed highly altered acetylation, succinylation and/or malonylation of proteins involved in these pathways in sirtuin-deficient mice. Here we investigate changes in the liver mitochondrial acetylome and succinylome in response to high-fat and sugar-based diets.