Practice question

Controlled nucleation lipid droplets depends ER resident seipin protein encoded BSCL2 mutated Berardinelli Seip congenital lipodystrophy type two characterized absence subcutaneous fat severe insulin resistance hypertriglyceridemia hepatic steatosis cardiomyopathy. Cryo EM recent shows seipin decameric ring ten transmembrane helices luminal beta sandwich domains binding anionic phospholipids phosphatidic acid phosphatidylinositol enriching TAG condensation ER junctions LD biogenesis sites demarcated by Pex30. Seipin cooperates LDAF1 LD assembly factor defining droplet biogenesis site facilitates neutral lipid flow ER membrane into lens prevents ectopic lens formation aberrant budding instability. Without seipin cells accumulate numerous tiny droplets clustered perinuclearly or occasional supersized droplets due unstable surface tension unregulated coalescence impaired maturation. Phospholipases hydrolyze phospholipids proteases degrade proteins kinases phosphorylate substrates none orchestrate lens budding efficiently. Yeast homolog Sei1 Fld1 interacts Pex30 Ldb16 Ldo45 controlling ER LD contacts size. Understanding seipin explains how droplet size number controlled metabolically linking ER morphology adipogenesis metabolic syndrome pathology tested advanced cell biology clinical genetics questions concerning organelle biogenesis lipid storage regulation adipose tissue development and therapeutic implications for lipodystrophy treatment strategies emerging.