Phosphoinositides in membrane remodeling during infections and cellular stresses

Abstract

Phosphoinositides, a versatile class of phosphorylated phosphatidylinositols, are emerging as central orchestrators of cellular stress responses. Beyond defining the organization and identity of endomembranes, these dynamic lipids act as highly adaptable signaling hubs that integrate diverse stress cues, from nutrient deprivation and mechanical strain to osmotic imbalance and DNA damage. Across evolution—from unicellular organisms to mammals—they drive conserved adaptation programs, including vacuolar remodeling, endosomal trafficking, and autophagosome biogenesis, through a finely tuned metabolism governed by an intricate network of kinases, phosphatases, and regulatory partners. Recent advances uncover how compartment-specific regulation, enzymatic diversity, and organelle crosstalk converge on phosphoinositide signaling, revealing these lipids as not only molecular adaptors but also promising therapeutic entry points in diseases marked by defective stress resolution. This review synthesizes emerging insights into the multifaceted roles of phosphoinositides in mobilizing membranes under stress, with a focus on mechanistic principles and recent research.