Chemical biology approaches for revealing interorganelle lipid transport pathways

Membranes are dynamic, lipid-rich structures that encapsulate cells and their organelle compartments. Understanding how lipids are metabolized, organized, and exchanged within tightly packed membrane environments requires robust strategies capable of mapping organelle-specific lipid networks and their associated protein machinery. Recent progress coming from the chemical biology arena has afforded a panoply of powerful and precise tools to probe lipids at the organelle level, enabling visualization, quantification, and manipulation of lipid pools with high spatiotemporal precision. These approaches include bespoke small-molecule chemical probes as well as designer engineered protein-based tools. We summarize recent progress across this technological landscape and highlight applications toward mapping enzymes and transporters that control organelle membrane lipid homeostasis. Together, these chemical strategies are expanding our ability to dissect lipid dynamics and providing new insights into fundamental cellular lipid homeostasis and related disease mechanisms.