NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes

• Published in: The Journal of biological chemistry Vol. 294; no. 5; pp. 1706 - 1709
• Main Author: Pfeffer, Suzanne R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2019; American Society for Biochemistry and Molecular Biology
• Subjects: Biological Transport; Carrier Proteins - genetics; Carrier Proteins - metabolism; cholesterol; Cholesterol - metabolism; cholesterol transport; cholesterol-binding protein; Hedgehog; Humans; Intracellular Signaling Peptides and Proteins; JBC Reviews; low-density lipoprotein (LDL); lysosome; lysosomes; Lysosomes - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mutation; Niemann-Pick C disease; Niemann-Pick Disease, Type C - physiopathology; NPC intracellular cholesterol transporter; NPC1; NPC2; Patched; sterol metabolism; transporter; cholesterol transport; NPC intracellular cholesterol transporter; Patched; Hedgehog; NPC1; NPC2; cholesterol-binding protein; transporter; cholesterol; Niemann-Pick C disease; sterol metabolism; lysosomes; lysosome; low-density lipoprotein (LDL)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.TM118.004165

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.