CDP-DAG synthase 1 and 2 regulate lipid droplet growth through distinct mechanisms.

摘要: Lipid droplets (LDs) are evolutionarily conserved organelles that play critical roles in mammalian lipid storage and metabolism. However, the molecular mechanisms governing biogenesis growth of LDs remain poorly understood. Phosphatidic acid (PA) is a precursor phospholipids triacylglycerols substrate CDP-diacylglycerol (CDP-DAG) synthase 1 (CDS1) CDS2, which catalyze formation CDP-DAG. Here, using siRNA-based gene knockdowns CRISPR/Cas9-mediated knockouts, along with immunological, molecular, fluorescence microscopy approaches, we examined role CDS1 CDS2 LD growth. Knockdown either or expression resulted giant supersized cultured cells. Interestingly, down-regulation cell death-inducing DFF45-like effector C (CIDEC), encoding prominent regulator adipocytes, restored size CDS1- but not CDS2-deficient On other hand, reducing two enzymes responsible for triacylglycerol synthesis, diacylglycerol O-acyltransferase 2 (DGAT2) glycerol-3-phosphate acyltransferase 4 (GPAT4), rescued phenotype CDS2-deficient, CDS1-deficient, Moreover, deficiency, promoted association DGAT2 GPAT4 impaired initial maturation. Finally, although both appeared to regulate PA levels on surface, had stronger effect. We conclude dynamics through distinct mechanisms.