Acetylation dynamics and stoichiometry in Saccharomyces cerevisiae

TY - JOUR

T1 - Acetylation dynamics and stoichiometry in Saccharomyces cerevisiae

AU - Weinert, Brian Tate

AU - Iesmantavicius, Vytautas

AU - Moustafa, Tarek

AU - Schölz, Christian

AU - Wagner, Sebastian A

AU - Magnes, Christoph

AU - Zechner, Rudolf

AU - Choudhary, Chuna Ram

PY - 2014/1/31

Y1 - 2014/1/31

N2 - Lysine acetylation is a frequently occurring posttranslational modification; however, little is known about the origin and regulation of most sites. Here we used quantitative mass spectrometry to analyze acetylation dynamics and stoichiometry in Saccharomyces cerevisiae. We found that acetylation accumulated in growth-arrested cells in a manner that depended on acetyl-CoA generation in distinct subcellular compartments. Mitochondrial acetylation levels correlated with acetyl-CoA concentration in vivo and acetyl-CoA acetylated lysine residues nonenzymatically in vitro. We developed a method to estimate acetylation stoichiometry and found that the vast majority of mitochondrial and cytoplasmic acetylation had a very low stoichiometry. However, mitochondrial acetylation occurred at a significantly higher basal level than cytoplasmic acetylation, consistent with the distinct acetylation dynamics and higher acetyl-CoA concentration in mitochondria. High stoichiometry acetylation occurred mostly on histones, proteins present in histone acetyltransferase and deacetylase complexes, and on transcription factors. These data show that a majority of acetylation occurs at very low levels in exponentially growing yeast and is uniformly affected by exposure to acetyl-CoA. Synopsis Characterization of the basic properties of acetylation in yeast cells by quantitative proteomics reveals distinct acetylation dynamics in different subcellular compartments and provides the first global analysis of acetylation stoichiometry. Acetylation is globally affected by metabolism and growth arrest. Mitochondrial proteins are acetylated within mitochondria. Most acetylation occurs at very low stoichiometry. High stoichiometry acetylation occurs on nuclear proteins. Characterization of the basic properties of acetylation in yeast cells by quantitative proteomics reveals distinct acetylation dynamics in different subcellular compartments and provides the first global analysis of acetylation stoichiometry.

AB - Lysine acetylation is a frequently occurring posttranslational modification; however, little is known about the origin and regulation of most sites. Here we used quantitative mass spectrometry to analyze acetylation dynamics and stoichiometry in Saccharomyces cerevisiae. We found that acetylation accumulated in growth-arrested cells in a manner that depended on acetyl-CoA generation in distinct subcellular compartments. Mitochondrial acetylation levels correlated with acetyl-CoA concentration in vivo and acetyl-CoA acetylated lysine residues nonenzymatically in vitro. We developed a method to estimate acetylation stoichiometry and found that the vast majority of mitochondrial and cytoplasmic acetylation had a very low stoichiometry. However, mitochondrial acetylation occurred at a significantly higher basal level than cytoplasmic acetylation, consistent with the distinct acetylation dynamics and higher acetyl-CoA concentration in mitochondria. High stoichiometry acetylation occurred mostly on histones, proteins present in histone acetyltransferase and deacetylase complexes, and on transcription factors. These data show that a majority of acetylation occurs at very low levels in exponentially growing yeast and is uniformly affected by exposure to acetyl-CoA. Synopsis Characterization of the basic properties of acetylation in yeast cells by quantitative proteomics reveals distinct acetylation dynamics in different subcellular compartments and provides the first global analysis of acetylation stoichiometry. Acetylation is globally affected by metabolism and growth arrest. Mitochondrial proteins are acetylated within mitochondria. Most acetylation occurs at very low stoichiometry. High stoichiometry acetylation occurs on nuclear proteins. Characterization of the basic properties of acetylation in yeast cells by quantitative proteomics reveals distinct acetylation dynamics in different subcellular compartments and provides the first global analysis of acetylation stoichiometry.

U2 - 10.1002/msb.134766

DO - 10.1002/msb.134766

M3 - Journal article

C2 - 24489116

SN - 1744-4292

VL - 10

SP - 716

JO - Molecular Systems Biology

JF - Molecular Systems Biology

IS - 1

ER -