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

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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Beavers WN,Rose KL,Galligan JJ,Mitchener MM,Rouzer CA,Tallman KA,Lamberson CR,Wang X,Hill S,Ivanova PT,Brown HA,Zhang B,Porter NA,Marnett LJ

doi

10.1021/acschembio.7b00480

subject

Has Abstract

pub_date

2017-08-18 00:00:00

pages

2062-2069

issue

8

eissn

1554-8929

issn

1554-8937

journal_volume

12

pub_type

杂志文章

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