2013/03/15 by Pushpendra Singh, Roopali Saxena, G. Srinivas +2 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Biochemistry #Biology #Biosynthesis #Cancer, Lipids, and Metabolism #Caveolin-1 and cellular processes #Cell biology #Chemistry #Cholesterol #Cholesterol and Lipid Metabolism #Enzyme #Homeostasis
paper · pdf · doi:10.1371/journal.pone.0058833
openalex publication_date 2013/03/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
The cell cycle is a ubiquitous, multi-step process that is essential for growth and proliferation of cells. The role of membrane lipids in cell cycle regulation is not explored well, although a large number of cytoplasmic and nuclear regulators have been identified. We focus in this work on the role of membrane cholesterol in cell cycle regulation. In particular, we have explored the stringency of the requirement of cholesterol in the regulation of cell cycle progression. For this purpose, we utilized distal and proximal inhibitors of cholesterol biosynthesis, and monitored their effect on cell cycle progression. We show that cholesterol content increases in S phase and inhibition of cholesterol biosynthesis results in cell cycle arrest in G1 phase under certain conditions. Interestingly, G1 arrest mediated by cholesterol biosynthesis inhibitors could be reversed upon metabolic replenishment of cholesterol. Importantly, our results show that the requirement of cholesterol for G1 to S transition is absolute, and even immediate biosynthetic precursors of cholesterol, differing with cholesterol merely in a double bond, could not replace cholesterol for reversing the cell cycle arrest. These results are useful in the context of diseases, such as cancer and Alzheimer's disease, that are associated with impaired cholesterol biosynthesis and homeostasis.