25-Hydroxycholesterol Increases the Availability of Cholesterol in Phospholipid Membranes

Journal Article · Tue Feb 01 04:00:00 EST 2011 · Biophysical Journal, 100(4):948-956

DOI:https://doi.org/10.1016/j.bpj.2010.12.3728· OSTI ID:1008221

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

Side-chain oxysterols are enzymatically generated oxidation products of cholesterol that serve a central role in mediating cholesterol homeostasis. Recent work has shown that side-chain oxysterols, such as 25-hydroxycholesterol (25-HC), alter membrane structure in very different ways from cholesterol, suggesting a possible mechanism for how these oxysterols regulate cholesterol homeostasis. Here we extend our previous work, using molecular dynamics simulations of 25-HC and cholesterol mixtures in 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers to examine interactions between 25-HC and cholesterol in the same bilayer. When added to cholesterol-containing membranes, 25-HC causes larger changes in membrane structure than when added to cholesterol-free membranes, demonstrating interactions between the two sterols. We also find that the presence of 25-HC changes the position, orientation, and solvent accessibility of cholesterol, shifting it into the water interface and therefore its availability to external acceptors. This is consistent with experimental results showing that oxysterols can trigger cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. These interactions provide a potential mechanism for 25-HC-mediated regulation of cholesterol trafficking and homeostasis through direct modulation of cholesterol availability.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1008221
• Report Number(s): PNNL-SA-73859
• Journal Information: Biophysical Journal, 100(4):948-956, Journal Name: Biophysical Journal, 100(4):948-956 Journal Issue: 4 Vol. 100; ISSN 0006-3495; ISSN BIOJAU
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AVAILABILITY
CHOLESTEROL
ENDOPLASMIC RETICULUM
HOMEOSTASIS
MEMBRANES
MIXTURES
MODULATION
ORIENTATION
OXIDATION
PHOSPHOLIPIDS
PLASMA
REGULATIONS
SOLVENTS
STEROLS
WATER
cholesterol
oxysterols
biomembranes
molecular dynamics