Localisation of oxysterols at the sub-cellular level and in biological fluids

Heraliyawala K Dias, Khushboo Borah, Berivan Amin, Helen Griffiths, Khouloud Sassi, Gérard Lizard, Ane Iriondo, Pablo Martinez-Lage

Research output: Contribution to journalReview article

Abstract

Oxysterols are oxidized derivatives of cholesterol that are formed enzymatically or via reactive oxygen species or both. Cholesterol or oxysterols ingested as food are absorbed and packed into lipoproteins that are taken up by hepatic cells. Within hepatic cells, excess cholesterol is metabolised to form bile acids. The endoplasmic reticulum acts as the main organelle in the bile acid synthesis pathway. Metabolised sterols originating from this pathway are distributed within other organelles and in the cell membrane. The alterations to membrane oxysterol:sterol ratio affects the integrity of the cell membrane. The presence of oxysterols changes membrane fluidity and receptor orientation. It is well documented that hydroxylase enzymes located in mitochondria facilitate oxysterol production via an acidic pathway. More recently, the presence of oxysterols was also reported in lysosomes. Peroxisomal deficiencies favour intracellular oxysterols accumulation. Despite the low abundance of oxysterols compared to cholesterol, the biological actions of oxysterols are numerous and important. Oxysterol levels are implicated in the pathogenesis of multiple diseases ranging from chronic inflammatory diseases (atherosclerosis, Alzheimer’s disease and bowel disease), cancer and numerous neurodegenerative diseases. In this article, we review the distribution of oxysterols in sub-cellular organelles and in biological fluids.
Original languageEnglish
Article number105426
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume193
Early online date10 Jul 2019
DOIs
Publication statusPublished - 1 Oct 2019

Bibliographical note

© 2019, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • Fluids
  • Membrane
  • Mitochondria
  • Oxysterols
  • Peroxisomes
  • Subcellular

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