J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M500143-JLR200 on July 16, 2005

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Journal of Lipid Research, Vol. 46, 2072-2082, October 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Intracellular trafficking of vitamin E in hepatocytes: the role of tocopherol transfer protein

Jinghui Qian*, Samantha Morley*, Kathleen Wilson*, Phil Nava{dagger}, Jeffrey Atkinson{dagger} and Danny Manor1,*

* Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853
{dagger} Department of Chemistry, Brock University, St. Catharines, Ontario, L2S 3A1, Canada

Published, JLR Papers in Press, July 16, 2005. DOI 10.1194/jlr.M500143-JLR200

1 To whom correspondence should be addressed. e-mail: dm43{at}cornell.edu

The term vitamin E denotes a family of tocopherols and tocotrienols, plant lipids that are essential for vertebrate fertility and health. The principal form of vitamin E found in humans, RRR-{alpha}-tocopherol (TOH), is thought to protect cells by virtue of its ability to quench free radicals, and functions as the main lipid-soluble antioxidant. Regulation of vitamin E homeostasis occurs in the liver, where TOH is selectively retained while other forms of vitamin E are degraded. Through the action of tocopherol transfer protein (TTP), TOH is then secreted from the liver into circulating lipoproteins that deliver the vitamin to target tissues. Presently, very little is known regarding the intracellular transport of vitamin E. We utilized biochemical, pharmacological, and microscopic approaches to study this process in cultured hepatocytes.

We observe that tocopherol-HDL complexes are efficiently internalized through scavenger receptor class B type I. Once internalized, tocopherol arrives within ~30 min at intracellular vesicular organelles, where it colocalizes with TTP, and with a marker of the lysosomal compartment (LAMP1), before being transported to the plasma membrane in a TTP-dependent manner. We further show that intracellular processing of tocopherol involves a functional interaction between TTP and an ABC-type transporter.

Supplementary key words antioxidants • lipid-transfer protein • lysosome


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