CoQ 10 selective miscibility and penetration into lipid monolayers with lower lateral packing density

CoQ is ubiquitously present in eukaryotic cells. It acts as electron carrier in the electron transport chain of the inner membrane of the mitochondria to facilitate aerobic cellular respiration. A highly stable lipid nanodispersion formulation containing CoQ (BPM31510) is currently in clinical inves...

Full description

Saved in:
Bibliographic Details
Published in:Biochimica et biophysica acta. Biomembranes 2017-07, Vol.1859 (7), p.1173-1179
Main Authors: Garg, Sumit, Swaminathan, Vandana, Dhavala, Sirisha, Kiebish, Michael A, Sarangarajan, Rangaprasad, Narain, Niven R
Format: Article
Language:English
Subjects:
Cell Membrane - chemistry
Lipids - chemistry
Solubility
Ubiquinone - analogs & derivatives
Ubiquinone - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:CoQ is ubiquitously present in eukaryotic cells. It acts as electron carrier in the electron transport chain of the inner membrane of the mitochondria to facilitate aerobic cellular respiration. A highly stable lipid nanodispersion formulation containing CoQ (BPM31510) is currently in clinical investigation for treatment of cancer. This study was designed to determine whether biophysical interactions between CoQ and lipid, in part, explain the observed stability and cellular accumulation of CoQ in cells and tissues. A lipid monolayer at the air-water interface was used as an experimental membrane model to measure CoQ penetration and solubility. Lipid monolayers with varying proportions of CoQ were laterally compressed to measure CoQ miscibility and lateral organization. Additionally, lipid monolayers with varying lateral packing densities were spread at the air-water interface and CoQ was injected in proximity to measure its rate of penetration. Our results demonstrate that CoQ selectively penetrates into lipid monolayers with a lower lateral packing density, and is excluded by monolayers of higher packing densities. Data also indicates that CoQ -lipid mixing is non-ideal. CoQ presence in lipid monolayers is biphasic, with one phase occupying the interstitial space between the DMPC lipids, and the other phase is present as pure CoQ domains. This work provides further insight into mechanism of action of CoQ based formulations that can significantly increase intracellular CoQ concentration to show pleotropic effects on cellular functions.
ISSN:0005-2736
DOI:10.1016/j.bbamem.2017.03.021