Sterols articles from across Nature Portfolio

The molecular mechanisms responsible for cellular cholesterol distribution remain unclear. Here, the authors identify a key role of lipid transfer proteins ORP9, OSBP, and GRAMD1s in maintaining cholesterol levels in the Golgi and plasma membrane.

Hendrix et al show that absence of hepatic Spring dramatically lowers levels of lipids in the liver and plasma in mice, and protects from development of diet-induced steatosis. In line, genetic variation in SPRING is associated with lipid levels in humans.

Cholesterol synthesis is highly oxygen consuming but how it is regulated by oxygen levels has not been clear. Here, Dickson et al. identify a HIF-independent, oxygen-sensing pathway for controlling cholesterol synthesis in human cells involving hypoxic-mediated degradation of SREBP2.

Production of highly modified sterols, such as cholesterol, is essential to eukaryotic physiology but has not been yet reported for bacteria. Here, Lee et al. show that a marine myxobacterium produces cholesterol, and provide evidence for further downstream modifications in this and other bacterial species.

Intracellular trafficking of cholesterol is essential for its uptake, storage and export. In this issue of Nature Metabolism, Xiao et al. provide powerful evidence for the importance of hepatic GRAMD1/Aster transporters in maintaining systemic cholesterol homeostasis.

The fungal sterol receptor and transcription factor Upc2 activates the transcription of ergosterol biosynthesis genes in response to ergosterol depletion in yeast. A structural and biochemical study reveals an Hsp90-dependent translocation activation mechanism of Upc2, with implications for triazole antifungal resistance.

Chemoproteomics-enabled identification of the targets of a hydroxylated cholesterol metabolite, 20(S)-hydroxycholesterol, reveals it to be the first reported endogenous ligand of the sigma-2 receptor, a drug target for neurodegeneration and neuropathic pain.

ORP2 is a lipid transfer protein that exchanges cholesterol for phosphatidylinositol-4,5-bisphosphate at the plasma membrane.