TY - JOUR
T1 - Triglyceride lipolysis triggers liquid crystalline phases in lipid droplets and alters the LD proteome
AU - Rogers, Sean
AU - Gui, Long
AU - Kovalenko, Anastasiia
AU - Zoni, Valeria
AU - Carpentier, Maxime
AU - Ramji, Kamran
AU - Mbarek, Kalthoum Ben
AU - Bacle, Amelie
AU - Fuchs, Patrick
AU - Campomanes, Pablo
AU - Reetz, Evan
AU - Speer, Natalie Ortiz
AU - Reynolds, Emma
AU - Thiam, Abdou Rachid
AU - Vanni, Stefano
AU - Nicastro, Daniela
AU - Mike Henne, W.
N1 - Publisher Copyright:
© 2022 Rogers et al.
PY - 2022/11/7
Y1 - 2022/11/7
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.202205053
DO - 10.1083/jcb.202205053
M3 - Article
C2 - 36112368
AN - SCOPUS:85138456621
SN - 0021-9525
VL - 221
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 11
M1 - e202205053
ER -