title: Endosomal cholesterol trafficking: protein factors at a glance.
abstract: The delivery of low-density lipoprotein-derived cholesterol (LDL-C) from endosomal compartments to the plasma membrane and the endoplasmic reticulum (ER) is an important yet poorly understood cellular process. Niemann-Pick C1 (NPC1), a multi-pass integral membrane protein on the limiting membranes of late endosomes (LE)/lysosomes (Ly), is known to insert lumenal LDL-C to the limiting membrane of LE/Ly. Recent progress has identified novel cytoplasmic proteins that regulate the exit of LDL-C from LE/Ly, such as ORP5, a member of the oxysterol-binding protein-related protein (ORPs) family, and Hrs/VPS27, a well-established regulator of the endosomal sorting complex required for transport pathway. Whereas ORP5/ORPs may serve as cytosolic cholesterol carriers and deliver cholesterol in a non-vesicular manner, how Hrs/VPS27 regulate endosomal cholesterol sorting remains enigmatic. We discuss the functional relationship between NPC1, Hrs, and ORP5, and formulate possible schemes on how LDL-C may be moved from endosomal compartments to other cellular organelles.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia.
authors.forename: Ximing
authors.initials: X
authors.lastname: Du
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D001692:Biological Transport; D002451:Cell Compartmentation; D002784:Cholesterol / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins; D002784:Cholesterol