{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:09:47Z","timestamp":1761394187979},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T00:00:00Z","timestamp":1339372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2012,9]]},"abstract":"The late endosomal\/lysosomal compartment (LE<\/jats:styled-content>\/LY<\/jats:styled-content>) plays a key role in sphingolipid breakdown, with the last degradative step catalyzed by acid ceramidase. The released sphingosine can be converted to ceramide in the ER<\/jats:styled-content> and transported by ceramide transfer protein (CERT<\/jats:styled-content>) to the Golgi for conversion to sphingomyelin. The mechanism by which sphingosine exits LE<\/jats:styled-content>\/LY<\/jats:styled-content> is unknown but Niemann\u2013Pick C1<\/jats:styled-content> protein (NPC1<\/jats:styled-content>) has been suggested to be involved. Here, we used sphingomyelin, ceramide and sphingosine labeled with [3<\/jats:sup>H<\/jats:styled-content>] in carbon\u20103 of the sphingosine backbone and targeted them to LE<\/jats:styled-content>\/LY<\/jats:styled-content> in low\u2010density lipoprotein (LDL<\/jats:styled-content>) particles. These probes traced LE<\/jats:styled-content>\/LY<\/jats:styled-content> sphingolipid degradation and recycling as suggested by (1) accumulation of [3<\/jats:sup>H<\/jats:styled-content>]\u2010sphingomyelin\u2010derived [3<\/jats:sup>H<\/jats:styled-content>]\u2010ceramide and depletion of [3<\/jats:sup>H<\/jats:styled-content>]\u2010sphingosine upon acid ceramidase depletion, and (2) accumulation of [3<\/jats:sup>H<\/jats:styled-content>]\u2010sphingosine\u2010derived [3<\/jats:sup>H<\/jats:styled-content>]\u2010ceramide and attenuation of [3<\/jats:sup>H<\/jats:styled-content>]\u2010sphingomyelin synthesis upon CERT<\/jats:styled-content> depletion. NPC1<\/jats:styled-content> silencing did not result in the accumulation of [3<\/jats:sup>H<\/jats:styled-content>]\u2010sphingosine derived from [3<\/jats:sup>H<\/jats:styled-content>]\u2010sphingomyelin\/LDL<\/jats:styled-content> or [3<\/jats:sup>H<\/jats:styled-content>]\u2010ceramide\/LDL<\/jats:styled-content>. Additional evidence against NPC1<\/jats:styled-content> playing a significant role in LE<\/jats:styled-content>\/LY<\/jats:styled-content> sphingosine export was obtained in experiments using the [3<\/jats:sup>H<\/jats:styled-content>]\u2010sphingolipids or a fluorescent sphingosine derivative in NPC1<\/jats:styled-content> knock\u2010out cells. Instead, NPC1<\/jats:styled-content>\u2010deficient cells displayed an increased affinity for sphingosine independently of protein\u2010mediated lipid transport. This likely contributes to the increased sphingosine content of NPC1<\/jats:styled-content> cells.<\/jats:bold><\/jats:p>","DOI":"10.1111\/j.1600-0854.2012.01379.x","type":"journal-article","created":{"date-parts":[[2012,5,18]],"date-time":"2012-05-18T13:09:43Z","timestamp":1337346583000},"page":"1234-1243","source":"Crossref","is-referenced-by-count":23,"title":["Tracking Sphingosine Metabolism and Transport in\u00a0Sphingolipidoses: NPC1<\/scp> Deficiency as a Test Case"],"prefix":"10.1111","volume":"13","author":[{"given":"Tomas","family":"Blom","sequence":"first","affiliation":[{"name":"Institute of Biomedicine, Anatomy, University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaiguo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Queens College, City University of New York Flushing NY 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