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Review
. 2015 Sep;14(9):2308-15.
doi: 10.1074/mcp.R114.046664. Epub 2015 Feb 25.

Metabolic Regulation by Lysine Malonylation, Succinylation, and Glutarylation

Matthew D Hirschey  1 , Yingming Zhao  2
Affiliations
Review

Metabolic Regulation by Lysine Malonylation, Succinylation, and Glutarylation

Matthew D Hirschey et al. Mol Cell Proteomics. 2015 Sep.

Abstract

Protein acetylation is a well-studied regulatory mechanism for several cellular processes, ranging from gene expression to metabolism. Recent discoveries of new post-translational modifications, including malonylation, succinylation, and glutarylation, have expanded our understanding of the types of modifications found on proteins. These three acidic lysine modifications are structurally similar but have the potential to regulate different proteins in different pathways. The deacylase sirtuin 5 (SIRT5) catalyzes the removal of these modifications from a wide range of proteins in different subcellular compartments. Here, we review these new modifications, their regulation by SIRT5, and their emerging role in cellular regulation and diseases.

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Figures

Fig. 1.
Fig. 1.
Protein acylation is balanced by KDACs and KATs. Protein acylation can be enzymatically catalyzed by lysine acyltransferases (KATs) and removed by lysine deacylases (KDACs).
Fig. 2.
Fig. 2.
Regulation of lysine malonylation, succinylation, and glutarylation. Lysine malonylation, succinylation, and glutarylation is targeted for removal by the NAD+-dependent deacylase SIRT5.
Fig. 3.
Fig. 3.
Metabolic regulation of malonyl-, succinyl-, and glutaryl-CoAs. Lipid, glucose, and amino acid metabolism all lead to the generation of acidic acyl-CoA species.
See this image and copyright information in PMC

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