Acidic anionic endosomal membranes

Acidic anionic endosomal membranes are specialized lipid bilayers that define the compartments of the endocytic pathway, specifically late endosomes and lysosomes. They are characterized by an acidic internal pH (typically 5.0–6.0) maintained by V-ATPase proton pumps and a unique lipid composition enriched with anionic lipids such as bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid [Huotari, J. & Helenius, A. (2011). EMBO J]. These membranes play a pivotal role in cellular homeostasis by regulating the sorting, trafficking, and degradation of internalized cargo. In pharmacology, they are a primary target for advanced drug delivery systems like lipid nanoparticles (LNPs) and cell-penetrating peptides, which utilize the acidic environment to trigger endosomal escape and deliver therapeutic payloads into the cytoplasm [Cullis, P. R. & Hope, M. J. (2017). Mol Ther]. Furthermore, many viruses exploit the low pH and specific lipid signatures of these membranes to undergo fusion and enter host cells, making them a critical focus for antiviral therapeutic strategies [Gruenberg, J. (2020). FEBS Lett].

Other names

Anionic endosomal membranesLate endosomal membranesAcidic endosomesEndolysosomal membranesBMP-enriched endosomal membranes

Interaction with acidic anionic endosomal membranes typically involves pH-dependent protonation of ionizable groups on the drug or delivery vehicle, which promotes electrostatic interaction with anionic lipids like bis(monoacylglycero)phosphate (BMP). This leads to membrane fusion or disruption (e.g., the proton sponge effect), facilitating the translocation of therapeutic cargo into the cytosol. Alternatively, pharmacological agents may inhibit V-ATPase to prevent acidification, thereby blocking viral entry or protein degradation [Cullis, P. R. & Hope, M. J. (2017). Mol Ther; Savarino, A., et al. (2003). Lancet Infect Dis].