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 - Funding Information:
W.M. Henne is supported by funds from the Welch Foundation (I-1873), the National Institutes of Health National Institute of General Medical Sciences (GM119768), National Institute of Diabetes and Digestive and Kidney Diseases (DK126887), Ara Parseghian Medical Research Fund, and the UT Southwestern Endowed Scholars Program. S. Rogers is supported in part by a National Institutes of Health T32 training grant (5T32GM008297).
Funding Information:
We thank Jonathan Friedman and the members of the Henne and Nicastro labs for helpful insights during this study. We thank Daniel Stoddard (UT Southwestern, Dallas, TX) for the management of the UT Southwestern electron microscope facilities and training, and Gang Fu for some data acquisition. The UT Southwestern Cryo-Electron Microscopy Facility is supported in part by the Cancer Prevention and Research Institute of Texas Core Facility Support Award RP170644. We would also like to thank the UT Southwestern proteomics and live cell imaging facilities for their assistance with data collection and analysis. Finally, we would like to thank Dr. Joel Goodman (UT Southwestern, Dallas, TX) for the Pln1 antibody. This research was supported in part by the computational resources provided by the BioHPC supercomputing facility located in the Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center.
Funding Information:
L. Gui, E. Reetz, and D. Nicastro are supported by the Cancer Prevention and Research Institute of Texas grant RR140082 to D. Nicastro. S. Vanni and V. Zoni acknowledge the support from the Swiss National Science Foundation (PP00P3_194807) and from grants from the Swiss National Supercomputing Centre under project ID s980 and s1131. A.R. Thiam is supported by Agence Nationale de la Recherche (ANR-18-CE11-0012-01-MOBIL and ANR-CE11-0032-02-LIPRODYN). The authors declare no competing financial interests.
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 -