Lysosomal membrane and acidic intracellular compartments

The lysosomal membrane and acidic intracellular compartments are specialized organelles characterized by an acidic internal pH (4.5–5.0) maintained by the action of vacuolar H+-ATPases (V-ATPases) (PMID: 17446867). These compartments serve as the primary site for macromolecular degradation, autophagy, and nutrient sensing via the mTORC1 pathway, acting as a metabolic signaling hub for the cell (PMID: 23698587). In pharmacology, these compartments are targeted through lysosomotropism, a process where weakly basic drugs accumulate in the acidic lumen via ion trapping (PMID: 4139131). This mechanism is utilized by drugs like hydroxychloroquine to modulate immune responses or inhibit viral entry, and by experimental anti-cancer agents to induce lysosomal membrane permeabilization (LMP), which triggers cathepsin-mediated programmed cell death (PMID: 18443626). Dysfunction of these compartments is a hallmark of lysosomal storage diseases and neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease, where impaired protein clearance leads to toxic aggregation (PMID: 23836233). Consequently, the lysosomal membrane is a focal point for developing therapies that either stabilize the membrane to prevent neurodegeneration or destabilize it to treat malignancy.

Other names

LysosomeAcidic organellesEndolysosomal systemVacuolar compartmentsAcidic intracellular compartments

Lysosomotropism (pH-driven accumulation via ion trapping), Lysosomal membrane permeabilization (LMP), Inhibition of vacuolar H+-ATPase (V-ATPase), and Inhibition of lysosomal acid hydrolases.