Cellular membrane and endosomal phospholipids (PL)

Cellular membrane and endosomal phospholipids are fundamental structural and functional lipids that constitute the bilayers of the plasma membrane and internal organelles. In the endosomal system, specific phospholipids like bis(monoacylglycero)phosphate (BMP) play a critical role in regulating internal membrane docking, fusion, and the sorting of proteins and lipids (Gruenberg, J., 2020, 'The endocytic pathway: a mosaic of domains'). These phospholipids serve as therapeutic targets for various pharmacological agents, including lysosomotropic drugs like chloroquine and hydroxychloroquine, which accumulate within endosomes and interfere with pH-dependent processes such as viral entry and antigen presentation (Al-Bari, M. A., 2017, 'Targeting lysosomes: A possible strategy for cancer therapy'). Additionally, certain antibiotics like daptomycin and polymyxins achieve their therapeutic effect by directly binding to and disrupting the integrity of bacterial phospholipids, leading to rapid cell death (Humphries, R. M., et al., 2013, 'Daptomycin: a novel lipopeptide antibiotic'). Beyond direct targeting, the composition of endosomal phospholipids is a key factor in the efficiency of lipid nanoparticle (LNP) delivery systems for mRNA vaccines and gene therapies, where endosomal escape is required for efficacy. Dysregulation of these lipids is a hallmark of lysosomal storage disorders and is increasingly implicated in the progression of neurodegenerative diseases and cancer (Chatman, K., et al., 2009, 'Phospholipidosis: review and perspectives').

Other names

Membrane lipidsEndosomal lipidsPhosphoglyceridesBis(monoacylglycero)phosphateLysobisphosphatidic acidPhosphatidylcholinePhosphatidylethanolaminePhosphatidylserine

Drugs targeting these molecules typically act through membrane disruption, alteration of endosomal pH (lysosomotropism), inhibition of viral-endosomal fusion, or sequestration of specific lipid species to disrupt signaling and trafficking pathways.