Eukaryotic cells produce over 1,000 different lipid species that tune organelle membrane properties, control signalling and store energy. Studying the biological functions of individual lipid has been challenging, owing to insufficient methodology for visualizing their intracellular localization, transport between organelles and interactions with proteins. Using minimally modified lipid probes, we set up an experimental platform for mechanistic lipid cell biology. We used this approach to measure transport rates for individual lipids in cellular assays and discovered that non-vesicular lipid transport is the primary mechanism that the cell uses to establish the distinct lipid compositions of organelle membranes.
We furthermore developed a workflow for mapping lipid-protein interactions as well as the biological activity of lipids during lipid trafficking. We found that integral membrane protein components of both the MICOS and NPC complexes are positioned in highly curved membranes by interactions with phosphatidylethanolamine lipids and discovered the likely disease mechanism of ether lipid deficiencies. We anticipate that chemical biology approaches will become an integral component of lipid biology and catalyse further discoveries in basic research and human physiology.
Dr. André Nadler conducts research at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany.
