How essential is cholesterol?
Cholesterol is an apparently indispensable lipid for numerous processes required for cell proliferation. Levels of this molecule are primarily regulated at the transcriptional level by the SREBPs (sterol-regulatory-element-binding proteins) and LXR (liver X receptor). In this issue of the Biochemical Journal, Rodríguez-Acebes et al. show that a cholesterol precursor, desmosterol, can support cell proliferation in the absence of cholesterol in a murine macrophage-like model (J774-D cells). These cells are defective in DHCR24 (sterol-Delta24-reductase, or 3beta-hydroxysterol Delta24-reductase), leading to desmosterol accumulation, and yet sterol homoeostasis appears to be normal with respect to SREBP processing and LXR activation. Other potentially cholesterol-dependent processes which were not the focus of this study are briefly discussed, such as lipid-raft-dependent cell signalling.
University of New South Wales, Sydney, Australia.
Julian
J
Stevenson
Andrew J
AJ
Brown
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003897:Desmosterol / Q000378:metabolism / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D000071518:Liver X Receptors; D008148:Lovastatin / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000071518:Liver X Receptors; D009419:Nerve Tissue Proteins; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D013261:Sterols; D003897:Desmosterol; D002784:Cholesterol; D008148:Lovastatin; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499056:Dhcr24 protein, mouse