Protein Modification by Endogenously Generated Lipid Electrophiles: Mitochondria as the Source and Target

ACS Chem Biol. 2017 Aug 18;12(8):2062-2069. doi: 10.1021/acschembio.7b00480. Epub 2017 Jun 28.


Determining the impact of lipid electrophile-mediated protein damage that occurs during oxidative stress requires a comprehensive analysis of electrophile targets adducted under pathophysiological conditions. Incorporation of ω-alkynyl linoleic acid into the phospholipids of macrophages prior to activation by Kdo2-lipid A, followed by protein extraction, click chemistry, and streptavidin affinity capture, enabled a systems-level survey of proteins adducted by lipid electrophiles generated endogenously during the inflammatory response. Results revealed a dramatic enrichment for membrane and mitochondrial proteins as targets for adduction. A marked decrease in adduction in the presence of MitoTEMPO demonstrated a primary role for mitochondrial superoxide in electrophile generation and indicated an important role for mitochondria as both a source and target of lipid electrophiles, a finding that has not been revealed by prior studies using exogenously provided electrophiles.

Publication types

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

MeSH terms

  • Animals
  • Lipid Peroxidation*
  • Lipids / chemistry*
  • Mitochondria / metabolism*
  • Molecular Structure
  • Protein Processing, Post-Translational*
  • Proteins / metabolism*
  • Signal Transduction


  • Lipids
  • Proteins