The nascent apoB100 polypeptide becomes associated with lipids transferred by MTP during its translocation across the ER membrane. When there is an insufficient level of either lipid synthesis or MTP activity, much of apoB100 gets shunted to the ERAD/proteasome pathway. The immature VLDL particles (pre-VLDL) are transported in vesicles to the Golgi, where they either 1) complete their maturation to fully lipidated VLDL particles, or 2) VLDL particles that fail to normally mature (because of metabolic circumstances, such as treatment with fish oils or insulin) get shunted from the Golgi to autophagosomes, which eventually fuse with lysosomes as part of autophagy. There is yet another opportunity to “intercept” VLDL particles before they enter the systemic circulation- namely at the cell surface through interactions with either LDL receptors or HSPGs, in a re-uptake process.
MTP, microsomal triglyceride transfer protein; PDI, protein disulfide isomerase; PERPP, post-ER, pre-secretory proteolysis; TG, triglyceride; VLDL, very low density lipoproteins.