Details

Autor(en) / Beteiligte

• Luo, Jie
• Jiang, Luyi
• Yang, Hongyuan
• Song, Bao‐Liang

Titel

Routes and mechanisms of post‐endosomal cholesterol trafficking: A story that never ends

Ist Teil von

• Traffic (Copenhagen, Denmark), 2017-04, Vol.18 (4), p.209-217

Ort / Verlag

Former Munksgaard: John Wiley & Sons A/S

Erscheinungsjahr

2017

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. Post‐endosomal cholesterol transport in a mammalian cell. Low‐density lipoprotein (LDL) particles are taken up via LDL receptor (LDLR)‐mediated endocytosis and delivered from early endosome (EE) to late endosome (LE)/lysosome (LY), during which LDL cholesteryl esters are hydrolyzed by acid lipase (AL) to release free cholesterol. Liberated cholesterol then exits LE/LY and moves to other organelles including the plasma membrane (PM), endoplasmic reticulum (ER), peroxisome (PERO), Golgi and mitochondria. These trafficking processes may involve nonvesicular transport at membrane contact sites formed by 2 closely apposed organelles. Upon reaching one membrane, cholesterol can be further delivered to another one, for example, the PM‐to‐ER retrograde cholesterol transport.