Metabolic Regulation by Lysine Malonylation, Succinylation, and Glutarylation

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acylation
  • Animals
  • Gene Expression Regulation
  • Humans
  • Intracellular Space / metabolism
  • Lysine / metabolism*
  • NAD / metabolism
  • Protein Processing, Post-Translational*
  • Proteins / metabolism*
  • Sirtuins / metabolism*


  • Proteins
  • NAD
  • SIRT5 protein, human
  • Sirtuins
  • Lysine