StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis.

How plasma membrane (PM) cholesterol is controlled is poorly understood. Ablation of the gene encoding the ER stress steroidogenic acute regulatory-related lipid transfer domain (StarD)5 leads to a decrease in PM cholesterol content, a decrease in cholesterol efflux, and an increase in intracellular neutral lipid accumulation in macrophages, the major cell type that expresses StarD5. ER stress increases StarD5 expression in mouse hepatocytes, which results in an increase in accessible PM cholesterol in WT but not in StarD5-/- hepatocytes. StarD5-/- mice store higher levels of cholesterol and triglycerides, which leads to altered expression of cholesterol-regulated genes. In vitro, a recombinant GST-StarD5 protein transfers cholesterol between synthetic liposomes. StarD5 overexpression leads to a marked increase in PM cholesterol. Phasor analysis of 6-dodecanoyl-2-dimethylaminonaphthalene fluorescence lifetime imaging microscopy data revealed an increase in PM fluidity in StarD5-/- macrophages. Taken together, these studies show that StarD5 is a stress-responsive protein that regulates PM cholesterol and intracellular cholesterol homeostasis.

Antibiotic Effects on Microbial Communities Responsible for Denitrification and N2O Production in Grassland Soils.

Antibiotics in soils may affect the structure and function of microbial communities. In this study, we investigated the acute effects of tetracycline on soil microbial community composition and production of nitrous oxide (N2O) and dinitrogen (N2) as the end-products of denitrification. Grassland soils were pre-incubated with and without tetracycline for 1-week prior to measurements of N2O and N2 production in soil slurries along with the analysis of prokaryotic and fungal communities by quantitative polymerase chain reaction (qPCR) and next-generation sequencing. Abundance and taxonomic composition of bacteria carrying two genotypes of N2O reductase genes (nosZ-I and nosZ-II) were evaluated through qPCR and metabolic inference. Soil samples treated with tetracycline generated 12 times more N2O, but N2 production was reduced by 84% compared to the control. In parallel with greater N2O production, we observed an increase in the fungi:bacteria ratio and a significant decrease in the abundance of nosZ-II carrying bacteria; nosZ-I abundance was not affected. NosZ-II-carrying Bacillus spp. (Firmicutes) and Anaeromyxobacter spp. (Deltaproteobacteria) were particularly susceptible to tetracycline and may serve as a crucial N2O sink in grassland soils. Our study indicates that the introduction of antibiotics to agroecosystems may promote higher N2O production due to the inhibitory effects on nosZ-II-carrying communities.