Fig. 1

Intracellular cholesterol homeostasis. When intracellular cholesterol levels are low, SREBP-2 is delivered to the Golgi where the active, N-terminal fragment is released and translocated to the nucleus where it activates the expression of cholesterol-related genes, such as HMGCR and the LDL receptor. The transcriptional activation of HGMCR leads to the de novo synthesis of cholesterol via the mevalonate pathway. The activation of the transcription of the LDLR leads to an increase in cellular cholesterol uptake through receptor-mediated endocytosis of LDL. When cholesterol levels are high, SREBP-2 is retained in the ER. In order to prevent over-accumulation of free cholesterol in the plasma and intracellular membranes, cholesterol is converted to cholesteryl esters primarily by the enzyme ACAT. Cholesteryl esters are stored as cytosolic lipid droplets. Excess cholesterol also generates oxysterols, natural ligands for LXRs. Their binding to LXRs activates the transcription of genes involved in cholesterol efflux, including ABCA1, ABCG1, and ABCG5/8. This figure was drawn by the author M. Feldt using the image bank of Servier Medical Art. URL to the images are https://smart.servier.com/category/cellular-biology/intracellular-components. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License. https://creativecommons.org/licenses/by/3.0/