Title | Protein Modification by Endogenously Generated Lipid Electrophiles: Mitochondria as the Source and Target. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Beavers WN, Rose KL, Galligan JJ, Mitchener MM, Rouzer CA, Tallman KA, Lamberson CR, Wang X, Hill S, Ivanova PT, H Brown A, Zhang B, Porter NA, Marnett LJ |
Journal | ACS Chem Biol |
Volume | 12 |
Issue | 8 |
Pagination | 2062-2069 |
Date Published | 2017 Aug 18 |
ISSN | 1554-8937 |
Keywords | Animals, Lipid Peroxidation, Lipids, Mitochondria, Molecular Structure, Protein Processing, Post-Translational, Proteins, Signal Transduction |
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. |
DOI | 10.1021/acschembio.7b00480 |
Alternate Journal | ACS Chem. Biol. |
PubMed ID | 28613820 |
Grant List | T32 GM065086 / GM / NIGMS NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:12pm