Side-chain oxysterols: From cells to membranes to molecules

Brett N. Olsen, Paul H. Schlesinger, Daniel S. Ory, Nathan A. Baker

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

This review discusses the application of cellular biology, molecular biophysics, and computational simulation to understand membrane-mediated mechanisms by which oxysterols regulate cholesterol homeostasis. Side-chain oxysterols, which are produced enzymatically in vivo, are physiological regulators of cholesterol homeostasis and primarily serve as cellular signals for excess cholesterol. These oxysterols regulate cholesterol homeostasis through both transcriptional and non-transcriptional pathways; however, many molecular details of their interactions in these pathways are still not well understood. Cholesterol trafficking provides one mechanism for regulation. The current model of cholesterol trafficking regulation is based on the existence of two distinct cholesterol pools in the membrane: a low and a high availability/activity pool. It is proposed that the low availability/activity pool of cholesterol is integrated into tightly packing phospholipids and relatively inaccessible to water or cellular proteins, while the high availability cholesterol pool is more mobile in the membrane and is present in membranes where the phospholipids are not as compressed. Recent results suggest that oxysterols may promote cholesterol egress from membranes by shifting cholesterol from the low to the high activity pools. Furthermore, molecular simulations suggest a potential mechanism for oxysterol "activation" of cholesterol through its displacement in the membrane. This review discusses these results as well as several other important interactions between oxysterols and cholesterol in cellular and model lipid membranes. This article is part of a Special Issue entitled: Membrane protein structure and function.

Original languageEnglish
Pages (from-to)330-336
Number of pages7
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1818
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Keywords

  • Cholesterol
  • Homeostasis
  • Molecular dynamics
  • Oxysterol
  • Sterol

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