FIGURE 1.

LD Biogenesis. From a biophysical perspective, LD biogenesis can be described as a four-step process. (A) Nucleation occurs when the ER bilayer saturates with NL, reaching a concentration in the bilayer to form lenses of the size in the order of nanometers. The PL composition and seipin among other proteins modulates this process through bilayer hydration, bending and curvature. (B) The individual lens growth takes place as newly synthesized NL are incorporated and by ripening and fusion between lenses; seipin prevents NL from shedding. (C) Budding is a spontaneous process (dewetting) driven by the interfacial tensions that come into play surrounding the droplet. The bilayer tension and the phospholipid asymmetry determine the sphericity and direction of budding, respectively. FIT has been recently proposed to be involved in the maintenance of the appropriate PL composition in each ER hemi-layer. (D) Although detachment is not to be expected for all LD, it is a reversible process. COPI has been proposed to be involved in the detachment/re-attachment process to the ER membrane. (E) Metabolic reactions more closely affecting NL synthesis and its modulating pathway SREBP. Note: the scheme represents a simplification of the metabolic vias according to the available evidence regarding the revised pathologies. For a more detailed description, see Pol et al. (2014).