Cholesterol: An evergreen molecule in biology

Abstract

Cholesterol, an essential component of higher eukaryotic membranes, was discovered more than two centuries ago. The development and progress of cholesterol research in the last 200 years has been truly fascinating, with elements of surprise, serendipity and intrigue. In this review, we trace this journey the way we see it, and follow it up with the role of membrane cholesterol in crucial areas of contemporary research (transbilayer domains, regulation of GPCR function and role in the entry of intracellular pathogens into host cells), with considerable footprint from our work. We believe that cholesterol will continue to surprise and fascinate future researchers, thereby justifying its evergreen nature. Abbreviations 7-DHC 7-dehydrocholesterol 7-DHCR 3β-hydroxy-steroid-7-reductase 25-NBD-cholesterol 25-[N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-methyl]amino]-27-norcholesterol CRAC cholesterol recognition/interaction amino acid consensus DHE dehydroergosterol (5,7,9(11)22-ergostatetraen-3β-ol) DPPC 1,2-dipalmitoyl-sn-glycero-3-phosphocholine FRAP fluorescence recovery after photobleaching GPCR G protein-coupled receptor NBD 7-nitrobenz-2-oxa-1,3-diazol-4-yl REES red edge excitation shift SLOS Smith-Lemli-Opitz syndrome 1. Cholesterol: An ancient molecule with a remarkable history Cholesterol was initially discovered as a component of human bile and gallstone sometime around 1760 AD by Poulletier de la Salle, a French physician and chemist (see Fig. 1) [13]. The naming of cholesterol was done by another French chemist Michel Chevreul in 1816. He named it cholesterine