ArticleMolecular biology of the cell2022
BORC-ARL8-HOPS ensemble is required for lysosomal cholesterol egress through NPC2.
Article in Molecular biology of the cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.Cell reports · 2026Article
- Pathogenic variants in BORCS5 cause a spectrum of neurodevelopmental and neurodegenerative disorders with lysosomal dysfunction.The Journal of clinical investigation · 2026Article
- NPC1 trafficking via VPS41-dependent LAMP carriers regulates endosomal cholesterol homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.bioRxiv : the preprint server for biology · 2025Article
- BLOC-1 and BORC: Complex regulators of endolysosomal dynamics.Cell chemical biology · 2025Review
- Structure of the endosomal CORVET tethering complex.Nature communications · 2024Article
- Loss of the HOPS complex disrupts early-to-late endosome transition, impairs endosomal recycling and induces accumulation of amphisomes.Molecular biology of the cell · 2024Article
- Niemann-Pick Disease Type C (NPDC) by Mutation ofAntioxidants (Basel, Switzerland) · 2023Review
- Inhibition of endolysosome fusion increases exosome secretion.The Journal of cell biology · 2023Article
- Consecutive functions of small GTPases guide HOPS-mediated tethering of late endosomes and lysosomes.Cell reports · 2023Article
- BORC complex specific components and Kinesin-1 mediate autophagy evasion by the autophagy-resistant Mycobacterium tuberculosis Beijing strain.Scientific reports · 2023Article
- The endo-lysosomal regulatory protein BLOC1S1 modulates hepatic lysosomal content and lysosomal lipolysis.Biochemical and biophysical research communications · 2023Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Lysosomes receive extracellular and intracellular cholesterol and redistribute it throughout the cell. Cholesterol egress from lysosomes is critical for cholesterol homeostasis, and its failure underlies the pathogenesis of genetic disorders such as Niemann-Pick C (NPC) disease. Here we report that the BLOC one-related complex (BORC)-ARL8-homotypic fusion and protein sorting (HOPS) ensemble is required for egress of free cholesterol from lysosomes and for storage of esterified cholesterol in lipid droplets. Depletion of BORC, ARL8, or HOPS does not alter the localization of the lysosomal transmembrane cholesterol transporter NPC1 to degradative compartments but decreases the association of the luminal transporter NPC2 and increases NPC2 secretion. BORC-ARL8-HOPS depletion also increases lysosomal degradation of cation-independent (CI)-mannose 6-phosphate (M6P) receptor (MPR), which normally sorts NPC2 to the endosomal-lysosomal system and then is recycled to the trans-Golgi network. These defects likely result from impaired HOPS-dependent fusion of endosomal-lysosomal organelles and an uncharacterized function of HOPS in CI-MPR recycling. Our study demonstrates that the BORC-ARL8-HOPS ensemble is required for cholesterol egress from lysosomes by enabling CI-MPR-dependent trafficking of NPC2 to the endosomal-lysosomal system.
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