Preprint Quantitative imaging of species-specific lipid transport in mammalian cells, 2024, Iglesias-Artola et al.

Quantitative imaging of species-specific lipid transport in mammalian cells
Juan M. Iglesias-Artola; Kai Schumann; Kristin Bohlig; H. Mathilda Lennartz; Milena Schumacher; Pavel Barahtjan; Cristina Jiminez Lopez; Radek Sachl; Karina Pombo-Garcia; Annett Lohmann; Petra Riegerova; Martin Hof; Bjorn Drobot; Andrej Shevchenko; Alf Honigmann; Andre Nadler

Eukaryotic cells produce over 1000 different lipid species which tune organelle membrane properties, control signalling and store energy. How lipid species are selectively sorted between organelles to maintain specific membrane identities is largely unknown due to the difficulty to image lipid transport in cells.

Here, we measured transport and metabolism of individual lipid species in mammalian cells using time-resolved fluorescence imaging of bifunctional lipid probes in combination with ultra-high resolution mass spectrometry and mathematical modelling. Quantification of lipid flux between organelles revealed that directional, non-vesicular lipid transport is responsible for fast, species-selective lipid sorting compared to slow, unspecific vesicular membrane trafficking.

Using genetic perturbations, we found that coupling between active lipid flipping and passive non-vesicular transport is a mechanism for directional lipid transport. Comparison of metabolic conversion and transport rates showed that non-vesicular transport dominates the organelle distribution of lipids while species-specific phospholipid metabolism controls neutral lipid accumulation.

Our results provide the first quantitative map of retrograde lipid flux in cells. We anticipate that our pipeline for quantitative mapping of lipid flux through physical and chemical space in cells will boost our understanding of lipids in cell biology and disease.


Link | PDF (Preprint: BioRxiv) [Open Access]