Host cell cholesterol homeostasis

Host cell cholesterol homeostasis represents the collective biochemical and cellular processes responsible for maintaining optimal cholesterol levels and distribution within the cell. This regulatory system involves a complex network of enzymes (e.g., HMG-CoA reductase), transporters (e.g., NPC1, NPC1L1, and ABCA1), and sensing proteins (e.g., SREBPs and SCAP) that coordinate cholesterol biosynthesis, uptake, efflux, and intracellular trafficking. Pharmacological modulation of this homeostasis is a cornerstone of cardiovascular therapy, primarily via statins and PCSK9 inhibitors, to lower systemic LDL cholesterol levels. Additionally, recent research identifies host cell cholesterol homeostasis as a critical host-directed target for antiviral and antibacterial therapies, as many pathogens hijack these lipid pathways for entry, replication, and egress. Consequently, perturbing the cellular cholesterol balance using repurposed drugs like itraconazole or fluoxetine has shown promise in reducing the infectivity of viruses such as Influenza A and SARS-CoV-2. While essential for metabolic health, drugs targeting this system must be monitored for side effects such as myopathy and liver enzyme elevation.

Other names

Cellular cholesterol metabolismIntracellular cholesterol traffickingLate endosomal/lysosomal (LEL) cholesterol balanceCholesterol homeostasisSterol regulatory pathway

Modulation of cholesterol levels through the inhibition of de novo biosynthesis (HMGCR), intestinal or cellular uptake (NPC1L1), or intracellular endosomal transport (NPC1) to maintain lipid balance or disrupt pathogen life cycles.