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. 2022 Jan 24;10:826379. doi: 10.3389/fcell.2022.826379

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Copyright © 2022 Islam, Hlushchenko and Pfisterer.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Multiple routes of endosomal cholesterol transport via membrane contact sites. LDL-derived cholesterol is liberated in late endosomes and lysosomes (LEL) and is made available to other cellular compartments via different mechanisms. Here we highlight several contact sites involved in this process. NPC1 via interaction with ORP5 or GramD1B can stimulate contacts between LELs and ER mediating cholesterol efflux to the ER. If NPC1 mediated export to the ER is impaired, cholesterol can be transferred to mitochondria via contacts established via StarD3. Also LELs can engage in contacts with peroxisomes and recycling endosomes for cholesterol export and cholesterol can be transported in reverse direction from ER to LEL.