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

William N. Beavers, Kristie L. Rose, James J. Galligan, Michelle M. Mitchener, Carol A. Rouzer, Keri A. Tallman, Connor R. Lamberson, Xiaojing Wang, Salisha Hill, Pavlina T. Ivanova, H. Alex Brown, Bing Zhang, Ned A. Porter, Lawrence J. Marnett

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2062-2069
Number of pages8
JournalACS Chemical Biology
Volume12
Issue number8
DOIs
StatePublished - Aug 18 2017
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Fingerprint

Dive into the research topics of 'Protein Modification by Endogenously Generated Lipid Electrophiles: Mitochondria as the Source and Target'. Together they form a unique fingerprint.

Cite this