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Non-enzymatic N-acetylation of Lysine Residues by AcetylCoA Often Occurs via a Proximal S-acetylated Thiol Intermediate Sensitive to Glyoxalase II

Lookup NU author(s): Dr Kurt Hoogewijs



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2017 The AuthorsAcetyl 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.

Publication metadata

Author(s): James AM, Hoogewijs K, Logan A, Hall AR, Ding S, Fearnley IM, Murphy MP

Publication type: Article

Publication status: Published

Journal: Cell Reports

Year: 2017

Volume: 18

Issue: 9

Pages: 2105-2112

Print publication date: 28/02/2017

Online publication date: 28/02/2017

Acceptance date: 03/02/2017

Date deposited: 08/05/2017

ISSN (electronic): 2211-1247

Publisher: Elsevier BV


DOI: 10.1016/j.celrep.2017.02.018


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