[Wang, Chao-Wen] Seipin negatively regulates sphingolipid production at the ER–LD contact site

Lipids are the basic components of the endomembrane system. Lipid synthesizing enzymes catalyze lipid synthesis mostly at the endoplasmic reticulum (ER), and the forming lipids are sorted through a complicated network to reach their final destination in the cell. It is conceivable that lipid synthesis is precisely controlled to cope with cell physiology. However, most of the mechanisms remain unclear. Our recent findings reveal that the human congenital generalized lipodystrophy (CGL) protein seipin regulates sphingolipid production at the contact site between ER and lipid droplets (LDs). Sphingolipids, essential components of the plasma membrane, are controlled by the cell to maintain homeostasis. Seipin interacts with two key enzymes of the sphingolipid synthesis pathways to inhibit their activities. When the cellular sphingolipid level is reduced, seipin dissociates from the two key enzymes, enabling the sphingolipid precursor termed ceramide being produced at the ER-LD contacts. The novel mechanism is published in the Journal of Cell Biology. Given that seipin is a disease-linked protein, further analysis is necessary to know whether the mechanism is involved in the etiology of the human CGL disease.