The IFN-γ-inducible GTPase IIGP1 regulates mitochondrial remodeling and immunometabolic reprogramming during inflammatory macrophage polarization

IIGP1 is a robustly IFN-{gamma}-induced protein in inflammatory macrophage polarization, and its loss significantly impairs iNOS induction and inflammatory remodeling.

• Why it matters: Inflammatory macrophage polarization depends on coordinated cytokine signaling, metabolic switching, and mitochondrial remodeling, but the molecular links between IFN-{gamma} signaling and mitochondrial homeostasis were unclear.
• What they did: Using quantitative mass spectrometry-based proteomics, the study identified IIGP1 as strongly induced and showed its expression depends on the IFN-{gamma}-JAK-STAT1 axis; IIGP1-deficient macrophages were then assessed for inflammatory markers, mitochondrial features, and bacterial killing.
• The result: IIGP1 associates with mitochondria, and its absence disrupts glycolytic reprogramming, redox adaptation, membrane potential regulation, structural remodeling, and intracellular killing of Escherichia coli and Salmonella Typhimurium.

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