MOF-mediated PRDX1 acetylation regulates inflammatory macrophage activation.

Area of Science:

• Cellular Biology
• Immunology
• Biochemistry

Background:

• Macrophage activation involves complex signaling pathways.
• Protein phosphorylation is crucial, but the role of acetylation in macrophage signal transduction is unclear.

Purpose of the Study:

• To investigate the role of protein acetylation in macrophage activation.
• To identify novel acetylation targets and their functions in inflammatory signaling.

Main Methods:

• Mass spectrometry to identify acetylated proteins.
• Western blotting to detect specific acetylation and phosphorylation.
• Cellular assays to measure reactive oxygen species and cytokine production.

Main Results:

• Peroxiredoxin 1 (PRDX1) was identified as a substrate of lysine acetyltransferase MOF.
• MOF acetylates PRDX1 at lysine 197 (K197), preventing its hyperoxidation and maintaining activity.
• Inflammatory stimulation with lipopolysaccharides (LPS) decreased PRDX1 K197 acetylation.
• Reduced PRDX1 K197 acetylation led to increased hydrogen peroxide, augmented ERK1/2 phosphorylation, stimulated glycolysis, and enhanced pro-inflammatory mediator (IL-6) production.

Conclusions:

• Redox protein acetylation, specifically of PRDX1, is a key regulator of inflammatory macrophage activation.
• Acetylation of PRDX1 coordinates transcriptional and metabolic programs during inflammation.
• This study reveals a novel mechanism linking redox signaling and acetylation in immune responses.