Published online before print May 6, 2004, doi: 10.1161/01.ATV.0000131264.66417.d5
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© 2004 American Heart Association, Inc.
Brief Reviews |
Intracellular Cholesterol Transport
From the Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY.
Correspondence Dr Jan L. Breslow, The Rockefeller University, 1230 York Avenue, New York, NY 10021. E-mail breslow{at}rockefeller.edu
Intracellular cholesterol transport is essential for the maintenance of cholesterol homeostasis. Many aspects of cholesterol metabolism are well-known, including its synthesis in the endoplasmic reticulum, its extracellular transport in plasma lipoproteins, its uptake by the low-density lipoprotein receptor, and its regulation of SREBP and LXR transcription factors. These fundamental pathways in cholesterol metabolism all rely on its proper intracellular distribution among subcellular organelles and the plasma membrane. Transport involving the ER and endosomes is essential for cholesterol synthesis, uptake, and esterification, whereas cholesterol catabolism by enzymes in mitochondria and ER generates steroids, bile acids, and oxysterols. Cholesterol is a highly hydrophobic lipid that requires specialized transport in the aqueous cytosol, involving either vesicles or nonvesicular mechanisms. The latter includes hydrophobic cavity transporters such as StAR-related lipid transfer (START) proteins. Molecular understanding of intracellular cholesterol trafficking has lagged somewhat behind other aspects of cholesterol metabolism, but recent advances have defined some transport pathways and candidate proteins. In this review, we discuss cholesterol transport among specific intracellular compartments, emphasizing the relevance of these pathways to cholesterol homeostasis.
Intracellular cholesterol transport is essential for the maintenance of cholesterol homeostasis. Many aspects of cholesterol metabolism are well-known, including its synthesis in the endoplasmic reticulum, its extracellular transport in plasma lipoproteins, its uptake by the low-density lipoprotein receptor, and its regulation of SREBP and LXR transcription factors. In this review, we discuss cholesterol transport among specific intracellular compartments, emphasizing the relevance of these pathways to cholesterol homeostasis.
Key Words: intracellular cholesterol transport • cholesterol metabolism • START proteins
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