title: Routes and mechanisms of post-endosomal cholesterol trafficking: A story that never ends.
abstract: Mammalian cells acquire most exogenous cholesterol through receptor-mediated endocytosis of low-density lipoproteins (LDLs). After internalization, LDL cholesteryl esters are hydrolyzed to release free cholesterol, which then translocates to late endosomes (LEs)/lysosomes (LYs) and incorporates into the membranes by co-ordinated actions of Niemann-Pick type C (NPC) 1 and NPC2 proteins. However, how cholesterol exits LEs/LYs and moves to other organelles remain largely unclear. Growing evidence has suggested that nonvesicular transport is critically involved in the post-endosomal cholesterol trafficking. Numerous sterol-transfer proteins (STPs) have been identified to mediate directional cholesterol transfer at membrane contact sites (MCSs) formed between 2 closely apposed organelles. In addition, a recent study reveals that lysosome-peroxisome membrane contact (LPMC) established by a non-STP synaptotagmin VII and a specific phospholipid phosphatidylinositol 4,5-bisphosphate also serves as a novel and important path for LDL-cholesterol trafficking. These findings highlight an essential role of MCSs in intracellular cholesterol transport, and further work is needed to unveil how various routes are regulated and integrated to maintain proper cholesterol distribution and homeostasis in eukaryotic cells.
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Jie
authors.identifier: 0000-0003-1899-3111
authors.initials: J
authors.lastname: Luo
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Luyi
authors.initials: L
authors.lastname: Jiang
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Song
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D013261:Sterols / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D013261:Sterols; D002784:Cholesterol
keywords: LPMC; NPC1; NPC2; cholesterol trafficking; late endosome; lysosome; membrane contact sites; nonvesicular transport; peroxisome; sterol transfer proteins; vesicular transport