25-HYDROXYCHOLESTEROL INDUCES REORGANIZATION OF LYSOSOMES IN NORMAL BUT NOT NIEMANN-PICK DISEASE TYPE-C ASTROCYTES

25-HYDROXYCHOLESTEROL (25-OHC), an oxysterol that potently regulates c ellular cholesterol metabolism, induced formation of novel fibrillar s tructures in normal mouse astrocytes as observed by fluorescence micro scopy with the cholesterol probe, filipin. These fibrils were identifi ed as lysosomes by their immunoreactivity for the lysosome associated membrane glycoprotein (LAMP). In contrast, astrocytes derived from the Niemann-Pick disease type C (NPC) mutant mouse were resistant to this oxysterol-induced lysosomal reorganization. NPC astrocytes have abnor mal intracellular cholesterol storage as observed by brightly positive filipin staining of their lysosomes. These results show that lysosoma l cholesterol storage in NPC astrocytes is associated with a block in oxysterol-mediated fibrillar reorganization of lysosomes.