NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes.
Low-density lipoprotein particles are taken up by cells and delivered to the lysosome where their cholesterol esters are cleaved off by acid lipase. The released, free cholesterol is then exported from lysosomes for cellular needs or storage. This article summarizes recent advances in our understanding of the molecular basis of cholesterol export from lysosomes. Cholesterol export requires NPC intracellular cholesterol transporter 1 (NPC1) and NPC2, genetic mutations of which can cause Niemann-Pick type C disease, a disorder characterized by massive lysosomal accumulation of cholesterol and glycosphingolipids. Analysis of the NPC1 and NPC2 structures and biochemical properties, together with new structures of the related Patched (PTCH) protein, provides new clues to the mechanisms by which NPC proteins may function.
['Pfeffer|Suzanne R|SR|']
D001692:Biological Transport D002352:Carrier Proteins D002784:Cholesterol D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D008247:Lysosomes D008562:Membrane Glycoproteins D009154:Mutation D000077296:Niemann-Pick C1 Protein D052556:Niemann-Pick Disease, Type C
NPC intracellular cholesterol transporter cholesterol cholesterol transport transporter lysosome lysosome NPC1 NPC2 Patched Hedgehog Niemann-Pick C disease cholesterol-binding protein low-density lipoprotein (LDL) lysosomes sterol metabolism