TMEM11-Dependent Cristae Architecture Restrains Imiquimod-Induced NLRP3 Inflammasome Activation via Mitochondrial ROS

TMEM11 loss in macrophages is linked to exaggerated caspase-1 activation and increased IL-1β/IL-18 secretion after imiquimod, driven by mitochondrial ROS.

• Why it matters: IMQ can trigger severe skin inflammation via NLRP3, but beyond complex I inhibition, the additional mitochondrial trigger—especially mtROS—has been disputed.
• What they did: Using Tmem11-deficient macrophages with MICOS-associated cristae defects, the study tested NLRP3 responses to canonical agonists and imiquimod, and applied antioxidant treatment to probe mtROS involvement.
• The result: Canonical agonist responses were normal, but imiquimod caused caspase-1 hyperactivation and heightened IL-1β/IL-18 that antioxidants rescued, implying cristae architecture restrains drug-induced mtROS to limit NLRP3 activation.

AI summary of the abstract · may contain errors · not medical advice · read the paper.