OSBP-related protein 2 is a sterol receptor on lipid droplets that regulates the metabolism of neutral lipids[S]

Riikka Hynynen; Monika Suchanek; Johanna Spandl; Nils Ba¨ck; Christoph Thiele; Vesa M. Olkkonen

Journal of Lipid Research (Jul 2009)

OSBP-related protein 2 is a sterol receptor on lipid droplets that regulates the metabolism of neutral lipids[S]

Riikka Hynynen,
Monika Suchanek,
Johanna Spandl,
Nils Ba¨ck,
Christoph Thiele,
Vesa M. Olkkonen

Affiliations

Riikka Hynynen: National Institute for Health and Welfare, and FIMM, Institute for Molecular Medicine Finland, Biomedicum, FI-00290 University of Helsinki, Helsinki, Finland; Max-Planck-Institute of Molecular Cell Biology and Genetics, D-01307 Dresden, Germany; Institute of Biomedicine/Anatomy, University of Helsinki, FI-00014 Helsinki, Finland; R. Hynynen and M. Suchanek contributed equally to this work
Monika Suchanek: National Institute for Health and Welfare, and FIMM, Institute for Molecular Medicine Finland, Biomedicum, FI-00290 University of Helsinki, Helsinki, Finland; Max-Planck-Institute of Molecular Cell Biology and Genetics, D-01307 Dresden, Germany; Institute of Biomedicine/Anatomy, University of Helsinki, FI-00014 Helsinki, Finland; R. Hynynen and M. Suchanek contributed equally to this work
Johanna Spandl: National Institute for Health and Welfare, and FIMM, Institute for Molecular Medicine Finland, Biomedicum, FI-00290 University of Helsinki, Helsinki, Finland; Max-Planck-Institute of Molecular Cell Biology and Genetics, D-01307 Dresden, Germany; Institute of Biomedicine/Anatomy, University of Helsinki, FI-00014 Helsinki, Finland; R. Hynynen and M. Suchanek contributed equally to this work
Nils Ba¨ck: National Institute for Health and Welfare, and FIMM, Institute for Molecular Medicine Finland, Biomedicum, FI-00290 University of Helsinki, Helsinki, Finland; Max-Planck-Institute of Molecular Cell Biology and Genetics, D-01307 Dresden, Germany; Institute of Biomedicine/Anatomy, University of Helsinki, FI-00014 Helsinki, Finland; R. Hynynen and M. Suchanek contributed equally to this work
Christoph Thiele: National Institute for Health and Welfare, and FIMM, Institute for Molecular Medicine Finland, Biomedicum, FI-00290 University of Helsinki, Helsinki, Finland; Max-Planck-Institute of Molecular Cell Biology and Genetics, D-01307 Dresden, Germany; Institute of Biomedicine/Anatomy, University of Helsinki, FI-00014 Helsinki, Finland; R. Hynynen and M. Suchanek contributed equally to this work
Vesa M. Olkkonen: National Institute for Health and Welfare, and FIMM, Institute for Molecular Medicine Finland, Biomedicum, FI-00290 University of Helsinki, Helsinki, Finland; Max-Planck-Institute of Molecular Cell Biology and Genetics, D-01307 Dresden, Germany; Institute of Biomedicine/Anatomy, University of Helsinki, FI-00014 Helsinki, Finland; R. Hynynen and M. Suchanek contributed equally to this work

Journal volume & issue: Vol. 50, no. 7
pp. 1305 – 1315

Abstract

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Oxysterol binding protein-related protein 2 (ORP2) is a member of the oxysterol binding protein family, previously shown to bind 25-hydroxycholesterol and implicated in cellular cholesterol metabolism. We show here that ORP2 also binds 22(R)-hydroxycholesterol [22(R)OHC], 7-ketocholesterol, and cholesterol, with 22(R)OHC being the highest affinity ligand of ORP2 (Kd 1.4 × 10−8 M). We report the localization of ORP2 on cytoplasmic lipid droplets (LDs) and its function in neutral lipid metabolism using the human A431 cell line as a model. The ORP2 LD association depends on sterol binding: Treatment with 5 μM 22(R)OHC inhibits the LD association, while a mutant defective in sterol binding is constitutively LD bound. Silencing of ORP2 using RNA interference slows down cellular triglyceride hydrolysis. Furthermore, ORP2 silencing increases the amount of [14C]cholesteryl esters but only under conditions in which lipogenesis and LD formation are enhanced by treatment with oleic acid. The results identify ORP2 as a sterol receptor present on LD and provide evidence for its role in the regulation of neutral lipid metabolism, possibly as a factor that integrates the cellular metabolism of triglycerides with that of cholesterol.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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