Protein Modification by Endogenously Generated Lipid Electrophiles: Mitochondria as the Source and Target
William N Beavers1, Kristie L Rose1, James J Galligan1
1A.B. Hancock Memorial Laboratory for Cancer Research, Departments of Chemistry, ‡Biochemistry, §Pharmacology, ∥Biomedical Informatics, ⊥Vanderbilt Mass Spectrometry Research Center, Vanderbilt Institute for Chemical Biology, Vanderbilt Center in Molecular Toxicology, Vanderbilt Ingram Cancer Center, Vanderbilt University , Nashville, Tennessee 37232, United States.
ACS Chemical Biology
|June 15, 2017
Summary
Oxidative stress causes lipid electrophile damage to proteins. This study reveals mitochondria are key sources and targets of this damage during inflammation, impacting membrane and mitochondrial proteins.
Area of Science:
- Biochemistry
- Cell Biology
- Oxidative Stress Research
Background:
- Lipid electrophiles cause protein damage during oxidative stress.
- Identifying protein targets of endogenous electrophiles is crucial for understanding disease.
Purpose of the Study:
- To conduct a systems-level survey of proteins adducted by endogenously generated lipid electrophiles during inflammation.
- To elucidate the role of mitochondria in the generation and targeting of lipid electrophiles.
Main Methods:
- Incorporation of ω-alkynyl linoleic acid into macrophage phospholipids.
- Activation of macrophages and subsequent protein extraction.
- Application of click chemistry and streptavidin affinity capture for target identification.
Main Results:
- Identified a significant enrichment of membrane and mitochondrial proteins as targets for lipid electrophile adduction.
- Demonstrated that MitoTEMPO significantly reduced adduction, highlighting the role of mitochondrial superoxide.
- Revealed mitochondria as both a source and target of lipid electrophiles, a novel finding.
Conclusions:
- Mitochondria play a critical role in generating and being targeted by lipid electrophiles during inflammation.
- This study provides new insights into the mechanisms of oxidative stress-induced cellular damage.
- Findings suggest mitochondria are central players in lipid electrophile-mediated protein damage.
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