Membrane editing with proximity labeling reveals regulators of lipid homeostasis

Cellular lipid metabolism is subject to strong homeostatic regulation, but the players involved in and mechanisms underlying these pathways remain largely uncharacterized. Here we develop a ‘feeding–fishing’ approach coupling membrane editing using optogenetic lipid-modifying enzymes (feeding) with organelle membrane proteomics through proximity labeling (fishing) to elucidate molecular players and pathways involved in the homeostasis of phosphatidic acid (PA), a multifunctional lipid central to glycerolipid metabolism. This approach identified several PA-metabolizing enzymes and lipid transfer proteins enriched in and depleted from PA-fed membranes. Mechanistic analysis revealed that PA homeostasis in the…

• LS
  Life Sciences Research Foundation
• HI
  Honjo International Scholarship Foundation
• NI
  National Institutes of Health

  Award: R01GM151682
• NS
  Natural Sciences and Engineering Research Council of Canada