Delayed lysosomal metabolism of lipids in mucolipidosis type IV fibroblasts after LDL-receptor-mediated endocytosis.

We specifically probed the low-density lipoprotein-receptor-dependent endosomal/lysosomal pathway of lipid degradation in control and mucolipidosis type IV fibroblasts using either [choline-methyl-14C]sphingomyelin in complex with apolipoprotein E, or cholesteryl [14C]oleate-labelled low-density lipoprotein as a substrate. Mucolipidosis type IV fibroblasts metabolized [14C]sphingomyelin and cholesteryl [14C]oleate significantly more slowly than controls and fibroblasts from patients with Hurler disease or Niemann-Pick disease type C. So far, no lysosomal enzyme deficiency has been reported for mucolipidosis type IV. Rather, the defect in mucolipidosis type IV cells has recently been suggested to be related to intracellular trafficking. Our results suggest that the defect in mucolipidosis type IV also affects the low-density lipoprotein-receptor-mediated endocytosis pathway.