Quantification of Mitochondrial Acetylation Dynamics Highlights Prominent Sites of Metabolic Regulation

Abstract

Background: Lysine acetylation, a prevalent post-translational modification, alters mitochondrial metabolism in response to nutrient changes. Results: Quantitative proteomics distinguishes dynamic and static acetylation sites, highlighting 48 likely regulatory sites of thousands identified. Conclusion: Acetylation of Acat1 lysine 260, a highly dynamic site, reversibly inhibits enzyme activity. Significance: Quantitative, state-specific proteomic analyses accelerate the functional characterization of acetylation in mitochondrial remodeling.

Sirtuin 3 (SIRT3) Protein Regulates Long-chain Acyl-CoA Dehydrogenase by Deacetylating Conserved Lysines Near the Active Site

“…A total of 15 different LCAD lysine residues have been reported as acetylated in mouse liver mitochondria (18,19,22,36). Including the SRM-MS results for Lys-318 presented here, four of these 15 lysines show significantly increased acetylation in SIRT3 knockout mice: Lys-81, Lys-318, Lys-322, and Lys-358 (18,22).…”

Hallmarks of a new era in mitochondrial biochemistry

“…Likewise, lysine acetylation has emerged as a prominent mitochondrial PTM. More than 2000 unique acetylation sites have now been identified, a number of which have been shown to participate in the regulation of pathways, including the urea cycle, fatty acid oxidation, ketogenesis, and the TCA cycle, among others (Kim et al 2006;Still et al 2013).…”

Influence of metformin on mitochondrial subproteome in the brain of apoE knockout mice

“…The increase of Acetyl-CoA acetyltransferase (ACAT2) may point to the improvement of mitochondrial performance by metformin, since ACAT is one of the major modulator of mitochondrial metabolism, a common link in many metabolic pathways, i.e. amino acid metabolism, fatty acid catabolism and ketogenesis (Still et al, 2013). In turn, the enzyme, D-3-phosphoglycerate dehydrogenase (3-PGDH), strongly up-regulated by metformin, catalyzes the first step of the L-serine synthesis pathway by oxidizing 3-phosphoglycerate to 3-phosphohydroxypyruvate using NAD + as a cofactor (Tabatabaie et al, 2010).…”