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MSRC Proteomics Core Laboratory

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

AUTHORS

Beavers WNWilliam N , Rose KLKristie L , Galligan JJJames J , Mitchener MMMichelle M , Rouzer CACarol A , Tallman KAKeri A , Lamberson CRConnor R , Wang XXiaojing , Hill SSalisha , Ivanova PTPavlina T , Brown HAH Alex , Zhang BBing , Porter NANed A , Marnett LJLawrence J . ACS chemical biology. 2017 6 28; 12(8). 2062-2069

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 Kdo-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.