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<p>The NLRP3 inflammasome has been shown to assemble on multiple organelles, including the mitochondria, endoplasmic reticulum, <i>trans</i>-Golgi network, and endosomes. Yet, the precise site of assembly remains unresolved. Emerging evidence suggests that membrane lipid composition may play a critical role with phosphoinositides, cholesterol, and cardiolipin, alongside membrane biophysical properties and cellular metabolic state, collectively shaping membranes where inflammasome assembles. Here, we review how lipid-dependent mechanisms regulate NLRP3 assembly across membranes and consider whether a defined membrane lipid signature governs inflammasome assembly. This understanding may have broader implications for therapeutic targeting in inflammatory and metabolic diseases.</p>

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Spatial control of NLRP3 inflammasome assembly by membrane lipid composition

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Paras K. Anand,
  • Najd M. Aljadeed

摘要

The NLRP3 inflammasome has been shown to assemble on multiple organelles, including the mitochondria, endoplasmic reticulum, trans-Golgi network, and endosomes. Yet, the precise site of assembly remains unresolved. Emerging evidence suggests that membrane lipid composition may play a critical role with phosphoinositides, cholesterol, and cardiolipin, alongside membrane biophysical properties and cellular metabolic state, collectively shaping membranes where inflammasome assembles. Here, we review how lipid-dependent mechanisms regulate NLRP3 assembly across membranes and consider whether a defined membrane lipid signature governs inflammasome assembly. This understanding may have broader implications for therapeutic targeting in inflammatory and metabolic diseases.