title: Translation inhibitors induce formation of cholesterol ester-rich lipid droplets.
abstract: Lipid droplets (LDs) in non-adipocytes contain triglycerides (TG) and cholesterol esters (CE) in variable ratios. TG-rich LDs are generated when unsaturated fatty acids are administered, but the conditions that induce CE-rich LD formation are less well characterized. In the present study, we found that protein translation inhibitors such as cycloheximide (CHX) induced generation of CE-rich LDs and that TIP47 (perilipin 3) was recruited to the LDs, although the expression of this protein was reduced drastically. Electron microscopy revealed that LDs formed in CHX-treated cells possess a distinct electron-dense rim that is not found in TG-rich LDs, whose formation is induced by oleic acid. CHX treatment caused upregulation of mTORC1, but the CHX-induced increase in CE-rich LDs occurred even when rapamycin or Torin1 was given along with CHX. Moreover, the increase in CE was seen in both wild-type and autophagy-deficient Atg5-null mouse embryonic fibroblasts, indicating that mTORC1 activation and suppression of autophagy are not necessary to induce the observed phenomenon. The results showed that translation inhibitors cause a significant change in the lipid ester composition of LDs by a mechanism independent of mTORC1 signaling and autophagy.
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohsaki
authors.forename: Tsuyako
authors.initials: T
authors.lastname: Tatematsu
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Takashi
authors.initials: T
authors.lastname: Maeda
authors.forename: Jinglei
authors.initials: J
authors.lastname: Cheng
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D050356:Lipid Metabolism / Q000187:drug effects*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes; D000070796:Perilipin-3; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
chemical_list: D002352:Carrier Proteins; D002788:Cholesterol Esters; D046912:Multiprotein Complexes; D000070796:Perilipin-3; C523440:Plin3 protein, mouse; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D003513:Cycloheximide; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases