Phospholipid demixing and the birth of a lipid droplet.
نویسندگان
چکیده
The biogenesis of lipid droplets (LD) in the yeast Saccharomyces cerevisiae was theoretically investigated on basis of a biophysical model. In accordance with the prevailing model of LD formation, we assumed that neutral lipids oil-out between the membrane leaflets of the endoplasmic reticulum (ER), resulting in LD that bud-off when a critical size is reached. Mathematically, LD were modeled as spherical protuberances in an otherwise planar ER membrane. We estimated the local phospholipid composition, and calculated the change in elastic free energy of the membrane caused by nascent LD. Based on this model calculation, we found a gradual demixing of lipids in the membrane leaflet that goes along with an increase in surface curvature at the site of LD formation. During demixing, the phospholipid monolayer was able to gain energy during LD growth, which suggested that the formation of curved interfaces was supported by or even driven by lipid demixing. In addition, we show that demixing is thermodynamically necessary as LD cannot bud-off otherwise. In the case of Saccharomyces cerevisiae our model predicts a LD bud-off diameter of about 12 nm. This diameter is far below the experimentally determined size of typical yeast LD. Thus, we concluded that if the standard model of LD formation is valid, LD biogenesis is a two step process. Small LD are produced from the ER, which subsequently ripe within the cytosol through a series of fusions.
منابع مشابه
Lipid droplet analysis in caveolin-deficient adipocytes: alterations in surface phospholipid composition and maturation defects[S]
Caveolins form plasmalemnal invaginated caveolae. They also locate around intracellular lipid droplets but their role in this location remains unclear. By studying primary adipocytes that highly express caveolin-1, we characterized the impact of caveolin-1 deficiency on lipid droplet proteome and lipidome. We identified several missing proteins on the lipid droplet surface of caveolin-deficient...
متن کاملPhosphatidylinositol-4,5-Bisphosphate Enhances Anionic Lipid Demixing by the C2 Domain of PKCα
The C2 domain of PKCα (C2α) induces fluorescence self-quenching of NBD-PS in the presence of Ca2+, which is interpreted as the demixing of phosphatidylserine from a mixture of this phospholipid with phosphatidylcholine. Self-quenching of NBD-PS was considerably increased when phosphatidylinositol-4,5-bisphosphate (PIP2) was present in the membrane. When PIP2 was the labeled phospholipid, in the...
متن کاملPhospholipase Lpl1 links lipid droplet function with quality control protein degradation
Protein misfolding is toxic to cells and is believed to underlie many human diseases, including many neurodegenerative diseases. Accordingly, cells have developed stress responses to deal with misfolded proteins. The transcription factor Rpn4 mediates one such response and is best known for regulating the abundance of the proteasome, the complex multisubunit protease that destroys proteins. Her...
متن کاملAnalysis of Lipid Droplet Proteins and their Contribution to Phospholipid Homeostasis during Lipid Droplet Expansion
متن کامل
Fabrication and characterisation of lavender oil - plant phospholipid based Sumatriptan succinate hybrid solid lipid nanoparticles.
Background: Nanostructured lipid carriers (NLCs) of sumatriptan succinate (SS) were prepared by using lavender oil. In ancient days, lavender oil was used for the treatment of a migraine. The natural anti-migraine agent, lavender oil, combined with an anti-migraine drug such as SS in a nano-formulation, will be a practical alternative approach in migraine therapy. Objective: NLCs of sumatri...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of theoretical biology
دوره 264 3 شماره
صفحات -
تاریخ انتشار 2010