Long-chain acyl-CoA synthetase 1 interacts with key proteins that activate and direct fatty acids into niche hepatic pathways.

摘要: Fatty acid channeling into oxidation or storage modes depends on physiological conditions and hormonal signaling. However, the directionality of this may also depend association each five acyl-CoA synthetase isoforms with specific protein partners. Long-chain synthetases (ACSLs) catalyze conversion long-chain fatty acids to acyl-CoAs, which are then either oxidized used in esterification reactions. In highly oxidative tissues, ACSL1 is located outer mitochondrial membrane (OMM) directs mitochondria for β-oxidation. liver, however, about 50% endoplasmic reticulum (ER) where its metabolic function unclear. Because hepatic partitioning likely require interaction other proteins, we an unbiased technique, BioID, discover ACSL1-binding partners hepatocytes. We targeted ER OMM Hepa 1–6 cells as a fusion Escherichia coli biotin ligase, BirA*. Proteomic analysis identified 98 proteins that specifically interacted at ER, 55 OMM, 43 common both subcellular locations. found subsets peroxisomal lipid droplet tethering vesicle uncovering dynamic role organelle interactions. Proteins involved metabolism were identified, including acyl-CoA–binding ceramide synthase 2 5. Our results provide fundamental detailed insights networks control metabolism.