Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey

Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Molecular Cell (Impact Factor: 14.02). 09/2006; 23(4):607-18. DOI: 10.1016/j.molcel.2006.06.026
Source: PubMed


Acetylation of proteins on lysine residues is a dynamic posttranslational modification that is known to play a key role in regulating transcription and other DNA-dependent nuclear processes. However, the extent of this modification in diverse cellular proteins remains largely unknown, presenting a major bottleneck for lysine-acetylation biology. Here we report the first proteomic survey of this modification, identifying 388 acetylation sites in 195 proteins among proteins derived from HeLa cells and mouse liver mitochondria. In addition to regulators of chromatin-based cellular processes, nonnuclear localized proteins with diverse functions were identified. Most strikingly, acetyllysine was found in more than 20% of mitochondrial proteins, including many longevity regulators and metabolism enzymes. Our study reveals previously unappreciated roles for lysine acetylation in the regulation of diverse cellular pathways outside of the nucleus. The combined data sets offer a rich source for further characterization of the contribution of this modification to cellular physiology and human diseases.

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    • "The role of acetylation in regulating chromatin structure and gene transcription is well studied with both lysine acetyltransferases and deacetylases taking part (Shahbazian & Grunstein, 2007). Mass spectrometry (MS), combined with acetylated peptide enrichment, has enabled the identification of thousands of acetylation sites on diverse proteins (Kim et al, 2006; Choudhary et al, 2009; Lundby et al, 2012), implicating acetylation in regulating various cellular processes. Metabolic proteins, particularly in mitochondria, were found to be frequently acetylated, and a multitude of studies have investigated the role of acetylation in regulating metabolism (Wang et al, 2010; Zhao et al, 2010; Newman et al, 2012). "
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    ABSTRACT: Acetylation is frequently detected on mitochondrial enzymes, and the sirtuin deacetylase SIRT3 is thought to regulate metabolism by deacetylating mitochondrial proteins. However, the stoichiometry of acetylation has not been studied and is important for understanding whether SIRT3 regulates or suppresses acetylation. Using quantitative mass spectrometry, we measured acetylation stoichiometry in mouse liver tissue and found that SIRT3 suppressed acetylation to a very low stoichiometry at its target sites. By examining acetylation changes in the liver, heart, brain, and brown adipose tissue of fasted mice, we found that SIRT3-targeted sites were mostly unaffected by fasting, a dietary manipulation that is thought to regulate metabolism through SIRT3-dependent deacetylation. Globally increased mitochondrial acetylation in fasted liver tissue, higher stoichiometry at mitochondrial acetylation sites, and greater sensitivity of SIRT3-targeted sites to chemical acetylation in vitro and fasting-induced acetylation in vivo, suggest a nonenzymatic mechanism of acetylation. Our data indicate that most mitochondrial acetylation occurs as a low-level nonenzymatic protein lesion and that SIRT3 functions as a protein repair factor that removes acetylation lesions from lysine residues.
    Full-text · Article · Sep 2015 · The EMBO Journal
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    • "Types of PTMs include reversible acetylation , phosphorylation, SUMOylation, glycosylation, and ubiquitination (Meek and Anderson, 2009; Zhao et al., 2011). Recently, acetylation and deacetylation of histones and nonhistone proteins have been shown to be involved in the control of cellular energy metabolism (Kim et al., 2006; Guan and Xiong, 2011). Protein acetylation on lysine residues is regulated by two types of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). "
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    ABSTRACT: Post-translational modifications (PTMs) of transcription factors play a crucial role in regulating metabolic homeostasis. These modifications include phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, and O-GlcNAcylation. Recent studies have shed light on the importance of lysine acetylation at nonhistone proteins including transcription factors. Acetylation of transcription factors affects subcellular distribution, DNA affinity, stability, transcriptional activity, and current investigations are aiming to further expand our understanding of the role of lysine acetylation of transcription factors. In this review, we summarize recent studies that provide new insights into the role of protein lysine-acetylation in the transcriptional regulation of metabolic homeostasis.
    Full-text · Article · Sep 2015 · Protein & Cell
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    • "Further analysis of the data revealed that total stretch of atp6 was 598 bp, which comprised of start codon and abbreviated stop codon (T). Presence of abbreviated stop codon in atp6 gene may be attributed as a consistent feature with annotation in the mt genomes of other ascaridoid nematodes (Okimoto et al. 1992, Lavrov and Brown 2001, Kim et al. 2006, Li et al. 2008 "

    Full-text · Dataset · Sep 2015
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