title: Active membrane cholesterol as a physiological effector.
abstract: Sterols associate preferentially with plasma membrane sphingolipids and saturated phospholipids to form stoichiometric complexes. Cholesterol in molar excess of the capacity of these polar bilayer lipids has a high accessibility and fugacity; we call this fraction active cholesterol. This review first considers how active cholesterol serves as an upstream regulator of cellular sterol homeostasis. The mechanism appears to utilize the redistribution of active cholesterol down its diffusional gradient to the endoplasmic reticulum and mitochondria, where it binds multiple effectors and directs their feedback activity. We have also reviewed a broad literature in search of a role for active cholesterol (as opposed to bulk cholesterol or lipid domains such as rafts) in the activity of diverse membrane proteins. Several systems provide such evidence, implicating, in particular, caveolin-1, various kinds of ABC-type cholesterol transporters, solute transporters, receptors and ion channels. We suggest that this larger role for active cholesterol warrants close attention and can be tested easily.
authors.affiliation: Department of Pathology, Rush University Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612, USA. Electronic address: ylange@rush.edu.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lange
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. Electronic address: tsteck@bsd.uchicago.edu.
authors.forename: Theodore L
authors.initials: TL
authors.lastname: Steck
mesh_terms: D018681:Anesthetics, General / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans
chemical_list: D018681:Anesthetics, General; D002784:Cholesterol
keywords: Active cholesterol; Channels; Homeostasis; Receptors; Transporters