Biophysical mechanisms of cholesterol synthesis and storage

Rachid Thiam

ENS-PSL, Laboratoire de physique de l’ENS, 24, rue Lhomond, 75231 Paris, France, thiam@phys.ens.fr

Cells store excess cholesterol as esters within lipid droplets, yet these lipids can form highly ordered phases. How such an order is accommodated within dynamic organelles remains unclear. We show that triglycerides are key to maintaining fluidity, allowing cholesterol ester incorporation and influencing the phase behavior of lipid droplet organelles. Instead of protein scaffolds alone, the balance and sequence of neutral lipid deposition, set at the endoplasmic reticulum, determine whether droplets stay fluid, enter mixed states, or become locked in liquid-crystalline phases. These ordered states prevent droplet ripening and reorganize the protein landscape at the organelles. In my presentation, I will share our recent advances in understanding the mechanisms of cholesterol synthesis and storage.

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