Title | Non-enzymatic N-acetylation of Lysine Residues by AcetylCoA Often Occurs via a Proximal S-acetylated Thiol Intermediate Sensitive to Glyoxalase II. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | James, AM, Hoogewijs, K, Logan, A, Hall, AR, Ding, S, Fearnley, IM, Murphy, MP |
Journal | Cell Rep |
Volume | 18 |
Issue | 9 |
Pagination | 2105-2112 |
Date Published | 2017 Feb 28 |
ISSN | 2211-1247 |
Abstract | Acetyl coenzyme A (AcCoA), a key intermediate in mitochondrial metabolism, N-acetylates lysine residues, disrupting and, in some cases, regulating protein function. The mitochondrial lysine deacetylase Sirtuin 3 (Sirt3) reverses this modification with benefits reported in diabetes, obesity, and aging. We show that non-enzymatic lysine N-acetylation by AcCoA is greatly enhanced by initial acetylation of a cysteine residue, followed by SN-transfer of the acetyl moiety to a nearby lysine on mitochondrial proteins and synthetic peptides. The frequent occurrence of an S-acetyl intermediate before lysine N-acetylation suggests that proximity to a thioester is a key determinant of lysine susceptibility to acetylation. The thioesterase glyoxalase II (Glo2) can limit protein S-acetylation, thereby preventing subsequent lysine N-acetylation. This suggests that the hitherto obscure role of Glo2 in mitochondria is to act upstream of Sirt3 in minimizing protein N-acetylation, thus limiting protein dysfunction when AcCoA accumulates. |
DOI | 10.1016/j.celrep.2017.02.018 |
Alternate Journal | Cell Rep |
Citation Key | 10.1016/j.celrep.2017.02.018 |
PubMed ID | 28249157 |
Grant List | MC_U105663142 / / Medical Research Council / United Kingdom |