Oxysterol sulfates in fluids, cells and tissues: how much do we know about their clinical significance, biological relevance and biophysical implications?

Oxysterol sulfates are emerging as key players in lipid homeostasis, inflammation and immunity. Despite this, knowledge on their basal levels in fluids, cells and tissues and any changes associated with age, gender and diet in health and disease; as well as their spatio-temporal distribution in cell membranes and organelles have been greatly hampered by the lack of commercially available pure synthetic standards. Expansion of the panel of pure oxysterol sulfates standards is pivotal to improve our understanding on the impact of oxysterol sulfates at the membrane level and their role in cellular events. While the clinical significance, biophysical implications and biological relevance of oxysterol sulfates in fluids, cells and tissues remains largely unknown, knowledge already gathered on the precursors of oxysterol sulfates (e.g. oxysterols and cholesterol sulfate) can be used to guide researchers on the most relevant aspects to search for when screening for oxysterol sulfates bioavailability in (patho)physiological conditions which are crucial in the design of biophysical and of cell-based assays. Herein, we provide a review on the brief knowledge involving oxysterol sulfate and an overview on the biophysical implications and biological relevance of oxysterols and cholesterol sulfate useful to redirect further investigations on the role of oxysterol sulfates in health and disease.