Triglyceride lipolysis triggers liquid crystalline phases in lipid droplets and alters the LD proteome

Sean Rogers, Long Gui, Anastasiia Kovalenko, Valeria Zoni, Maxime Carpentier, Kamran Ramji, Kalthoum Ben Mbarek, Amelie Bacle, Patrick Fuchs, Pablo Campomanes, Evan Reetz, Natalie Ortiz Speer, Emma Reynolds, Abdou Rachid Thiam, Stefano Vanni, Daniela Nicastro, W. Mike Henne

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Lipid droplets (LDs) are reservoirs for triglycerides (TGs) and sterol-esters (SEs), but how these lipids are organized within LDs and influence their proteome remain unclear. Using in situ cryo-electron tomography, we show that glucose restriction triggers lipid phase transitions within LDs generating liquid crystalline lattices inside them. Mechanistically this requires TG lipolysis, which decreases the LD's TG:SE ratio, promoting SE transition to a liquid crystalline phase. Molecular dynamics simulations reveal TG depletion promotes spontaneous TG and SE demixing in LDs, additionally altering the lipid packing of the PL monolayer surface. Fluorescence imaging and proteomics further reveal that liquid crystalline phases are associated with selective remodeling of the LD proteome. Some canonical LD proteins, including Erg6, relocalize to the ER network, whereas others remain LD-associated. Model peptide LiveDrop also redistributes from LDs to the ER, suggesting liquid crystalline phases influence ER-LD interorganelle transport. Our data suggests glucose restriction drives TG mobilization, which alters the phase properties of LD lipids and selectively remodels the LD proteome.

Original languageEnglish (US)
JournalThe Journal of cell biology
Volume221
Issue number11
DOIs
StatePublished - Nov 7 2022

ASJC Scopus subject areas

  • Cell Biology

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