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    J Lipid Res. 2009 Jul;50(7):1305-15. Epub 2009 Feb 17.

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

    Hynynen R, Suchanek M, Spandl J, Bäck N, Thiele C, Olkkonen VM.

    Source

    National Institute for Health and Welfare, University of Helsinki, Helsinki, Finland.

    Abstract

    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 (K(d) 1.4 x 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 microM 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 [(14)C]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.

    PMID:
    19224871
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2694330
    Free PMC Article

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