Endogenous sterol intermediates of the mevalonate pathway regulate HMGCR degradation and SREBP-2 processing.

Sterol-regulated HMG-CoA reductase (HMGCR) degradation and SREBP-2 cleavage are two major feedback regulatory mechanisms governing cholesterol biosynthesis. Reportedly, lanosterol selectively stimulates HMGCR degradation, and cholesterol is a specific regulator of SREBP-2 cleavage. However, it is unclear whether other endogenously generated sterols regulate these events.

[Applications of machine learning in clinical decision support in the omic era].

With the development of the omic technologies, the acquisition approaches of various biological data on different levels and types are becoming more mature. As a large amount of data will be produced in the process of diagnosis and treatment of diseases, it is necessary to utilize the artificial intelligence such as machine learning to analyze complex, multi-dimensional and multi-scale data and to construct clinical decision support tools. It will provide a method to figure out rapid and effective programs in diagnosis and treatment.

PIP4K2A regulates intracellular cholesterol transport through modulating PI(4,5)P homeostasis.

The transport of LDL-derived cholesterol from lysosomes to peroxisomes is facilitated by membrane contacts formed between the lysosomal protein synaptotagmin VII and the peroxisomal lipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P]. Here, we used RNA interference to search for regulators of PI(4,5)P and to study the effects of altered PI(4,5)P homeostasis on cholesterol transport. We found that knockdown of phosphatidylinositol 5-phosphate 4-kinase type-2 α (PIP4K2A) reduced peroxisomal PI(4,5)P levels, decreased lysosome-peroxisome membrane contacts, and increased accumulation of lysosomal cholesterol in human SV-589 fibroblasts.