Endocytosis of very low density lipoprotein remnants by liver of fasted rats.

Radioactive lipoproteins in the very low density lipoprotein (VLDL) density range were taken up by rat liver in vivo. The radioactivity became associated with an intracellular particle of d = 1.11 that did not correspond to lysosomes, endoplasmic reticulum, or plasma membrane as determined by marker enzyme distribution. Radioactive VLDL remnants could be released from these particles by passage through a hydraulic press, hypotonic shock, or sonication. The release of radioactivity from the particles by one of these methods became more complete with increasing time after injection. The injection of colchicine inhibited the breakdown of the VLDL triglyceride and cholesterol ester and caused an accumulation of radioactive material in the d = 1.11 particles. In contrast, injected chloroquine inhibited breakdown of VLDL triglyceride and cholesterol ester and caused an accumulation in lysosomes. We have concluded VLDL remnants are metabolized in liver by an endocytosis-lysosomal digestion pathway and that the d = 1.11 particles are endocytic vesicles. The existence of a releasable pool of VLDL within endocytic vesicles makes it possible to examine the internalized remnant.